This single-arm, multicenter phase II study enrolled patients with SCLC or extrathoracic small-cell primaries and 1–10 brain metastases to evaluate rates of neurologic death following treatment with SRS/SRT relative to historical WBRT-treated controls.

Neurologic death was defined as substantial radiographic intracranial progression associated with corresponding neurologic symptoms, in the absence of systemic disease progression or life-threatening systemic symptoms. Among the 100 patients treated, the median number of brain metastases was 2 (IQR 1–4; range 1–10). Median overall survival was 10.2 months, and only 22% required salvage WBRT. A total of 20 neurologic deaths and 64 non-neurologic deaths were reported. The 1-year neurologic death rate was 11.0% (95% CI, 5.8–18.1), notably lower than the historical rate of 17.5% in patients receiving WBRT.

This prospective analysis demonstrates that SRS/SRT is associated with low rates of neurologic death in patients with SCLC and limited brain metastases who undergo diligent post-treatment surveillance. These findings support the emerging role of stereotactic approaches as a viable alternative to WBRT in this historically challenging population and warrant continued evaluation in future studies.

Reference (Pub-Med Link): Aizer AA, Tanguturi SK, Shi DD, et al. Stereotactic radiosurgery in patients with small cell lung cancer and 1-10 brain metastases: A multi-institutional, phase ii, prospective clinical trial. J Clin Oncol 2025;43:2986-2997. https://doi.org/10.1200/jco-25-00056

Key Institution: Brigham and Women’s Hospital, Dana-Farner Cancer Institute, Multi-institutional

Keywords: Small cell lung cancer, Brain Mets

August 7,2025

No early toxicity seen in heterogenous dose escalation for locally advanced non -small cell lung cancer

Phase III multicenter dose-escalation trial to assess toxicity and local control (though only toxicity reported at this time) for dose escalation in locally advanced NSCLC. Patients included in the trial were ECOG 0-1, stage IIB-IIIB, and feasibility of delivering 66Gy/33fx. 350 patients were randomly assigned to SOC of 66Gy vs heterogeneous dose-escalation up to 95Gy. 2 treatment plans were developed for each patient (one standard dose, the other dose escalated as much as possible) prior to randomization. The plans had to be isotoxic, meaning the dose-escalation plans had to have lung v20 within 20% and a mean lung dose within 1Gy. Esophgus D1cc <70-74Gy, airways and vessels D1cc<74Gy. Mean tumor dose in dose escalated arm was 88Gy. There was no difference in early toxicity between the two arms. Grade 2 esophagitis during radiotherapy was 28.1% and 25.6%, grade 3 esophagitis 7.3% and 4.1%, grade 2 pneumonitis 15.7% and 20.3%, and grade 3 pneumonitis 3.9% and 5.8% in standard and escalated arms, respectively.  

Reference (Pub-Med Link): Schytte T, Knap MM, Kristiansen C, et al. Toxicity within 6 months of heterogeneous fluorodeoxyglucose-guided radiotherapy dose escalation for locally advanced non-small cell lung cancer in the scandinavian randomized phase iii narlal2 trial. J Clin Oncol 2025;43:1972-1983. https://doi.org/10.1200/jco-24-01386

Key Institution: Odense University Hospital, Multi-institutional

Keywords: Advanced non -small cell lung cancer

Current staging systems and the definitions of oligometastasis continue to evolve. In this study, the investigators evaluated the metastatic burden of 120 patients from 2016-2019 with a non-small cell lung cancer primary and metastatic disease. The purpose of the study is to evaluate baseline patient factors, systemic local therapy, extent and location of metastatic lesions, and survival outcomes. Using current clinical trial definitions of oligometastasis, the authors sought to evaluate how many patients within this cohort would have “qualified” for an oligomet clinical trial, characterized the patterns of metastasis, and sought how many were treated in such a manner similar to those qualified for current oligometastatic trials.

Among the 120 patients evaluated, 75% had presented with metastasis at the time of initial diagnosis (denovo) and there was a median of 4 metastatic lesions that involved 3 organ systems. Of this cohort, more than a third (37.5%) were eligible for at least 1 oligometastatic trial. Of those considered oligometastatic, 44.4% received local therapy and less than a third (28.9%) underwent ablative terapy to all sites, highlighting the non-aggressive approaches to oligometastatic disease. There was a trend towards greater OS (44.4 vs 24.9 months; P = .055) and progression-free survival (8.0 vs 5.4 months; P = .06) in patients meeting eligibility for at least 1 oligometastatic trial. By adding malignant pleural effusions and early progression as exclusionary criteria, only 54.1% of patients with ≤3 synchronous metastases were eligible for consideration of local therapy. Early progression on systemic therapy was associated with worse survival (10.0 vs 42.4 months; P < .001), whereas presence of malignant pleural effusions was not.

This study highlights the need for consensus on the definitions for oligometastasis and the lack of ablative local therapy employment in these situations. It appears use of early progression as an exclusionary criterion for oligometastasis-directed treatments is warranted.

Reference (Pub-Med Link): No, H. J., Raja, N., Von Eyben, R. et al. (2022). Characterization of Metastatic Non-Small Cell Lung Cancer and Oligometastatic Incidence in an Era of Changing Treatment Paradigms. International Journal of Radiation Oncology, Biology, Physics, 114(4), 603–610. https://doi.org/10.1016/j.ijrobp.2022.04.050

Key Institution: Stanford
Keywords: Mets, Lung

This article aimed to analyze the prognostic/predictive benefit of immunotherapy medication against programmed death ligand 1 (PD-L1) expression among patients with stage III non-small cell lung cancer (NSCLC). In order to accomplish this, a total of 312 patients with stage III NSCLC that were treated with definitive chemoradiation and adjuvant durvalumab were analyzed from 2017-2021. Among this group, pretreatment tumor PD-L1 expression was quantified. Progression-free survival (PFS) and overall survival (OS) in PD-L1 expression subgroups (<1%, 1%-49%, and 50%-100%) were compared against a subset of patient (994 patients) with stage III NSCLC that were treated definitively with chemoradiation but without adjuvant durvalumab. PD-L1 expression was <1%, 1% to 49%, and 50% to 100% in 109 (34.9%), 96 (30.7%), and 107 (34.3%) patients, respectively. As PD-L1 expression increased, a longer PFS (P=0.003) and OS were seen (P= .036). In comparing PFS and OS from the group that did receive durvalumab against the group of patients that did not receive durvalumab, PFS was longer for PD-L1 50% to 100% (P < .001) and PD-L1 1% to 49% (P = .003) but not PD-L1 <1% (P = .19); positive results favoring the group that received durvalumab. Similar results were found for OS, with no significant difference between the no-durvalumab group and PD-L1 <1% (P= .22). As such, this analysis was able to conclude that the finding of increasing tumor PD-L1 expression was a positive prognostic factor in patients with stage III NSCLC treated with adjuvant durvalumab.

Reference (Pub-Med Link):  Bryant, A. K., Sankar, K., Strohbehn, G. W., et al.  (2022). Prognostic and Predictive Role of PD-L1 Expression in Stage III Non-small Cell Lung Cancer Treated With Definitive Chemoradiation and Adjuvant Durvalumab. International Journal of Radiation Oncology, Biology, Physics, 113(4), 752–758. https://doi.org/10.1016/j.ijrobp.2022.03.015

Key Institution: University of Michigan

Keywords: Lung

This article notes that the clinical spectrum of COVID19 ranged from asymptomatic to acute respiratory distress syndrome (ARDS) and sequential organ failure (SOF) as a result of cytokine storm. ARDS requires supplemental oxygen and mechanical ventilator support; despite these measures, mortality is high for patients with severe disease. 

The article reviews the pathogenesis of COVID-19 and describes in some detail the effects of a hyperinflammatory state caused by the virus. It also provides some historical prior studies including a 2013 review of low dose radiation therapy to treat pneumonia during the 20th century; this review reported that about 700 patients with pneumonia were effectively treated with low-dose RT. The present paper reviewed that radiation therapy can induce an anti-inflammatory response that could theoretically be achieved with low doses of radiation therapy (0.3-0.5 Gy in a single fraction).

This article was certainly interesting and provided some historical context that radiation therapy has been used to treat pneumonias in the past, although the quality of evidence is quite low by modern standards and at best this review is hypothesis-generating. More specific preclinical work should be done.

(Open Access)

Reference (PubMed Link): Dhawan G, Kapoor R, Dhawan R, et al. Low dose radiation therapy as a potential life saving treatment for covid-19-induced acute respiratory distress syndrome (ards). Radiother Oncol 2020;147:212-216.

Key Institution: University of Massachusetts
Keywords: Radiation Therapy, COVID-19, ARDS 

SARS-CoV-2, the virus that causes COVID-19, has been responsible for nearly 500,000 deaths worldwide. Prior studies have shown that patients with comorbidities who develop COVID-19 have a higher risk of poor outcomes. Some studies have shown that patients with malignancy, in particular, are at-risk.

The authors of this study retrospectively examined patients who tested positive for COVID-19 and had previously received radiation therapy for malignancy between March 14, 2020 and April 15, 2020 at Montefiore Medical Center. They identified 107 patients: 26% had malignancies of the breast, 25% prostate, 13% lung, 7% gynecologic, 6% head and neck, 4% blood, and 21% other. The primary study outcome was overall survival from the time of the positive COVID-19 test.

The median follow-up was 7 days from the date of diagnosis for patients alive with COVID-19. 24 patients had passed away at the time of the analysis. The actuarial 14-day survival rate was 66%. Increasing mean lung dose, a diagnosis of lung cancer, and having receiving radiation therapy one month and one year before the positive COVID-19 test were all linked to a higher risk of death. The authors noted that their “survival model demonstrates a near linear relationship between mortality risk after COVID-19 diagnosis and mean lung radiation therapy dose.”

In sum, in this single institution retrospective study, the authors found that patients with a history of radiation therapy who were diagnosed with COVID-19 had a 66% 14-day actuarial survival. The authors also found a nearly linear relationship between mean lung dose from radiation therapy and mortality after being diagnosed with COVID-19. However, these results be must be further validated before drawing more generalized conclusions.

(Open Access)

Reference (PubMed Link): Kabarriti R, Brodin NP, Maron MI, et al. Extent of prior lung irradiation and mortality in covid-19 patients with a cancer history. Adv Radiat Oncol 2020;5:707-710.

Key Institution: Montefiore Medical Center
Keywords: COVID-19, Lung Irradiation, mortality