This study is a secondary dosimetric analysis of the ASPIRE-ILD phase 2 trial, which prospectively treated medically inoperable patients with early-stage non-small cell lung cancer (NSCLC ) and...

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

Phase III randomized trial of 172 evaluable patients with locally advanced, inoperable non-small cell lung cancer treated with chemoradiation randomly assigned to radiation treatment planning with target volume delineation based on 1) PET and CT (conventional planning) vs 2) PET alone (PET planning). IMRT and 3DCRT were permitted. Both groups were dose-escalated to 60 to 74 Gy to the primary tumor and affected nodal levels. All patients received concurrent platinum-based doublet chemotherapy. Noninferiority study with primary outcome of time to locoregional progression. At 29 months median follow-up, risk of locoregional recurrence was noninferior in the PET planning group compared to the conventional planning group on both intention-to-treat and per-protocol analyses: per-protocol, PET 14% vs conventional 29%; in intention-to-treat, PET 17% vs conventional 30%. Toxicity rates were similar between groups. Conclusion: PET-based planning offers similar (possibly improved) local control outcomes compared to conventional PET- and CT-based planning, with similar toxicity. 

Reference (PubMed Link): Nestle U, Schimek-Jasch T, Kremp S, et al. Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (pet-plan): A multicentre, open-label, randomised, controlled trial. Lancet Oncol 2020;21:581-592.

Key Institution: Multi-Institutional
Keywords: Lung cancer, NSCLC, PET-CT

This was a post hoc exploratory analysis of the PACIFIC trial of unresectable stage III NSCLC, which showed a PFS and OS benefit with adjuvant durvalumab after chemoradiation. PFS favored durvalumab regardless of PD-L1 expression level (>= 25%, 1-24%, <1%, unknown). However, the benefit was not statistically significant for patients with <1% PD-L1 as the 95% CI crossed 1 (HR 0.73, 95% CI 0.48-1.11). OS favored durvalumab for PD-L1 expression >= 25%, 1-24%, and unknown, but not for <1% (HR 1.14, 95% 0.71-1.84). Also, the benefit was not statistically significant for patients with PD-L1 1-24%, as the 95% CI crossed 1 (HR 0.67, 95% CI 0.41-1.10). It was noted that due to few events, OS analysis for PD-L1 <1% may be under-powered.

A strength of this study is that PFS was determined by blinded central review. The major limitation is that this was a post hoc exploratory analysis: PD-L1 expression testing was not mandated, only 63% of patients had available PD-L1 expression, and PD-L1 was not used to stratify the randomization to durvalumab vs placebo. Thus, it is potentially subject to bias and confounding, since PD-L1 status may not have been missing at random, and there were noted to be imbalances in baseline characteristics between the durvalumab vs placebo arms depending on PD-L1 level.

Overall, this hypothesis-generating analysis supports use of PD-L1 in all patients, at least for its PFS benefit. 

Reference (PubMed Link): Paz-Ares L, Spira A, Raben D, et al. Outcomes with durvalumab by tumour pd-l1 expression in unresectable, stage iii non-small-cell lung cancer in the pacific trial. Ann Oncol 2020.

Key Institution: Multi-institutional
Keywords: Radiation, chemoradiation, immunotherapy, durvalumab, adjuvant, PACIFIC, NSCLC 

Radical treatment of metastases with stereotactic body radiation therapy (SBRT) is commonly implemented in patients receiving concurrent immune checkpoint inhibition (ICI), despite limited safety and toxicity data.

Records from a single academic institution were reviewed to identify patients treated with lung SBRT and concurrent (within 30 days) ICI; a contemporaneous cohort receiving lung SBRT alone was included for reference.

All patients received RT per RTOG 0813. Patients were treated with lung SBRT between June 2012 and January 2019. Fifty-six treatment courses, corresponding to 69 target lesions across 54 patients, were identified from those receiving lung SBRT with concurrent immunotherapy. Sixty-eight courses of treatment across 63 patients (79 target lesions) were included, comprising the SBRT-alone cohort.

The incidence of acute AEs, occurring predominantly during SBRT delivery, was similar between the SBRT + ICI and SBRT-alone groups.  However, SBRT + ICI patients were more likely to have treatment-related AEs up to 90 days after SBRT; grade 3 (G3) or higher subacute toxicity was seen in 26.8% versus 2.9% of patients (P < .001). Severe (G3 or higher) pneumonitis was substantially higher when concurrent ICI was given (10.7% vs 0%, P Z .007).

The risk of any-grade pneumonitis appeared elevated with ICI/ICI combination therapy (62.5% vs 29.17%, P Z .105); however, the risk of high-grade pneumonitis was similar compared with other ICI treatment types (12.5% vs 10.42%). ICI administration between SBRT treatment days was safe; it did not appear to increase the risk of high-grade or any-grade pneumonitis over non-overlapping delivery.

The prevalence of clinically significant pneumonitis was approximately 10%, as reported here. This risk, among known risk factors, should be considered when assessing immunotherapy patients for SBRT candidacy

Reference (PubMed Link): Tian S, Switchenko JM, Buchwald ZS, et al. Lung stereotactic body radiation therapy and concurrent immunotherapy: A multicenter safety and toxicity analysis. Int J Radiat Oncol Biol Phys 2020.

Key Institution: Multi-Institutional
Keywords: SBRT, Lung, Immunotherapy, Pneumonitis 

In patients with advanced NSCLC, concurrent chemoradiation and immunotherapy with durvalumab is standard care per the PACIFIC trial.  This retrospective review of patients with stage III unresectable NSCLC highlights similar efficacy and toxicity in clinical practice as within the PACIFIC trial.  Importantly, the presentation of distant progression was oligometastatic disease in 47% which informs the use of oligometastatsis-directed therapy including SBRT.  In this subset, PD-L1 and tumor mutational burden did not predict improvement in outcomes.  This study represents an important detailed analysis of patients receiving chemoradiotherapy with durvalumab, with the important factor of oligometastatic distant metastases highlighted.

Reference (PubMed Link): Offin M, Shaverdian N, Rimner A, et al. Clinical outcomes, local-regional control and the role for metastasis-directed therapies in stage iii non-small cell lung cancers treated with chemoradiation and durvalumab. Radiother Oncol 2020;149:205-211.

Key Institution: Memorial Sloan Kettering
Keywords: Radiotherapy, immunotherapy, NSCLC, durvalumab, metastases 

RTOG 0617 compared standard-dose (60 Gy) with high-dose (74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC). This was a report of long-term outcomes. Median follow-up was 5.1 years. There were 3 grade 5 adverse events in the standard arm and 9 in the high dose arm. Treatment-related grade >=3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the standard arm v 12.1% and 17.4% in the high dose arm, respectively (P = .0005 and .0001). There was no difference in pulmonary toxicity, with grade >=3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months (P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% (P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. 

This was a large multi-center randomized trial examining the benefit of two methods of treatment intensification for advanced NSCLC. Notably the trial preceded the PACIFIC trial, which established chemoradiation with adjuvant immunotherapy as the new standard of care for this disease state. Unfortunately, neither method of treatment intensification (cetuximab or dose-escalated radiation) succeeded in improving outcomes and these strategies may have even worsened outcomes. The exact reason for this remains uncertain, though differences in heart dose may partially explain this. 

Overall, this was a well-designed randomized trial, which importantly demonstrates the challenges of improving outcomes in NSCLC through treatment intensification. While the addition of immunotherapy to chemoradiation has been shown to be beneficial for patients with this condition, the results of RTOG 0617 suggest that efforts to make further outcome improvements should proceed with caution.  

Reference (PubMed Link): Bradley JD, Hu C, Komaki RR, et al. Long-term results of nrg oncology rtog 0617: Standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable stage iii non-small-cell lung cancer. J Clin Oncol 2020;38:706-714.

Key Institution: Multi-Institutional
Keywords: NSCLC, randomized trial, treatment intensification, dose escalation, cetuximab 

Twenty-one participants had locally advanced, unresectable, stage III NSCLC, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate hematologic, renal, and hepatic function.

Pembrolizumab was combined with concurrent chemoradiotherapy (weekly carboplatin and paclitaxel with 60 Gy of radiation in 2 Gy per d). Progression-free survival was good, with relatively few serious immune-related adverse events.

Consolidative immunotherapy following chemoradiation for locally advanced NSCLC was shown to improve survival in the PACIFIC trial. The use of concurrent immunotherapy with radiation in intriguing but there is little data regarding safety and efficacy. This Phase 1 study demonstrates that concurrent chemoimmunoradiotherapy is tolerable in this population, with further studies required to evaluate efficacy.

(Open Access)

Reference (PubMed Link): Jabbour SK, Berman AT, Decker RH, et al. Phase 1 trial of pembrolizumab administered concurrently with chemoradiotherapy for locally advanced non-small cell lung cancer: A nonrandomized controlled trial. JAMA Oncol 2020;6:1-8.

Key Institution: Multi-Institutional (Royal Marsden Hospital, Institute of Cancer Research, London, UK)
Keywords: Immunotherapy, Chemoradiotherapy, Locally Advanced Non-small Cell Lung Cancer 

The dosing for stage III non-small cell lung cancer has been established at 60Gy since RTOG 7301. Trialists looked to dose escalation as a possibility, comparing 74Gy to60Gy in 2Gy fractions together with carboplatin paclitaxel. There was also a cetuximab component to the 2x2 trial. The 2015 publication of two-year follow-up results showed decreased overall survival with the dose escalation arm (median survival 28.7mo vs 20.3 mo). The use of cetuximab conferred additional toxicity without any overall survival difference. Updated five-year follow up confirmed these findings with the standard arm having better 5yr survival (32% vs 23%). Interestingly, even local failure trended to improvement with the standard lower dose. There was some speculation as to whether treatment noncompliance with the high dose arm contributed to the worse outcomes, but there was no difference when analyzing only the protocol compliant population. Multivariate analysis points to cardiac dose as a potential culprit for the decreased survival, but this still doesn’t explain the trend towards decreased local control.

(Open Access)

Reference (PubMed Link): Bradley JD, Hu C, Komaki RR, et al. Long-term results of NRG oncology RTOG 0617: Standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable stage iii non-small-cell lung cancer. J Clin Oncol 2019:Jco1901162.

Key Institution: Multi-Institutional (US, Canada)
Keywords: Clinical practice, nonsmall cell lung cancer, dose-escalation, cetuximab, RTOG, NRG Oncology

This multi-institutional phase 2 study randomized 92 patients with advanced non-small cell lung cancer (NSCLC) regardless of PD-L1 status. Pembrolizumab was either given along (control arm) or after radiotherapy (8 Gy x 3) to a single tumor site. The main outcome was improvement in overall response rate (ORR). 76 patients were randomized to the control arm and 36 to the experimental arm. The ORR at 12 weeks was 18% in the control arm vs 36% in the experimental arm (P = 0.07). Median progression-free survival was 1.9 months vs 6.6 months (P = 0.19). No increase in treatment-related toxic effects was observed in the experimental arm. The study concluded that stereotactic body radiotherapy prior to pembrolizumab was well tolerated, and suggested that a larger trial is necessary to determine whether radiotherapy may activate noninflamed NSCLC towards a more inflamed tumor microenvironment. 

Reference (PubMed Link): Theelen W, Peulen HMU, Lalezari F, et al. Effect of pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone on tumor response in patients with advanced non-small cell lung cancer: Results of the pembro-rt phase 2 randomized clinical trial. JAMA Oncol 2019.

Key Institution: Multi-Institutional (The Netherlands)
Keywords: Non-small cell lung cancer, pembrolizumab, stereotactic body radiotherapy 

This prospective clinical study of patients receiving SABR for lung cancer set out to test the hypothesis that apparent diffusion coefficient (ADC) on MRI imaging is a useful radiomic marker of locoregional failure. ADC in this context is thought to be a marker of increased cellularity potentially indicative of persistent tumor.

The investigators took baseline MRI ADC measurements pre-treatment and then again at one month post-treatment. All patients were being treated with thoracic SABR for early-stage (12 patients) or oligometastatic (1 patient) NSCLC. Images were analyzed by 2 blinded radiologists, and results were highly concordant between the 2 (Pearson Correlation <0.85). They found a mean 18% increase in ADC from pre to post treatment. Interestingly, only 2 of their patients experienced locoregional failure, and both of these patients exhibited a 1 month post-treatment ADC increase of >40%, whereas 0/10 recurrence-free patients broke this 40% cutoff. This effect was found to be statistically significant. 

Post-SABR changes in lung anatomy and associated fibrosis are a major limitation of interpreting post-treatment tumor response. Indeed, tumors may be obscured by areas of inflammatory consolidation. PET scan does little to address this limitation, as inflammatory areas are often PET-positive. In that context, the present study is among the first to evaluate MRI radiomic assessment of treatment response and correlate this to patient outcomes. Their result is certainly interesting in that they were able to show a cut point of the data which correctly assigned 100% of their patients into future recurrence or not. 

Although this was a well-designed prospective trial, the obvious limitation of this study is sample size. The study was closed early due to poor accrual. An additional potential limitation only partially addressed by the authors is that MRI is a historically limited modality to evaluate the thorax. However, the use of breathhold imaging allowed for usable data for the study. 

Although this is certainly an interesting result, it is hypothesis-generating and not hypothesis-testing. Indeed, it is premature to make major clinical determinations based on an absolute number of 2 recurrence events. More prospective studies are needed to evaluate this finding further, testing whether the observed predictive value for recurrence persists in larger patient populations. It is plausible that application of these findings in future can lead to early intervention and personalized adaptive therapy in the immediate post-SABR period before traditional methodology would detect treatment failure.

Reference (PubMed Link): Sampath S, Rahmanuddin S, Sahoo P, et al. Change in apparent diffusion coefficient is associated with local failure after stereotactic body radiation therapy for non-small cell lung cancer: A prospective clinical trial. Int J Radiat Oncol Biol Phys 2019;105:659-663.

Key Institution: University of Iowa
Keywords: NSCLC, SABR, apparent diffusion coefficient, MRI

This is a phase II multi-institutional randomized trial evaluating single fraction SBRT 30 Gy versus three fraction 60 Gy for peripheral NSCLC in medically inoperable patients. The primary endpoint of this study was grade three or higher thoracic toxicity and other adverse events. Secondary endpoints included local control, progression free survival, overall survival, and quality of life. 

From 2008 to 2015, 98 patients were randomized and reported with 53.8 months median follow up. There were ten patients lost to follow up, 9 of which were on the three fraction arm.  

For the primary endpoint, 16% on the single fraction arm and 12% on the three fraction arm experienced a grade three thoracic adverse event, no grade 4-5 were reported. There were no statistically significant differences in local control, progression free survival, and overall survival endpoints. The OS at 2 years was 73% versus 62% and PFS at 2 years was 65% versus 50% for single and three fraction arms, respectively.  On quality of life questionnaires patients in the single fraction arm reported significantly better dyspnea at six months and better social functioning at three and six months. There was no change in pulmonary function tests compared with baseline in both arms. 

In conclusion, this is a phase II randomized study compared single versus three fraction SBRT for peripheral NSCLC in medically inoperable patients. The primary endpoint, grade 3 thoracic adverse events, was not significantly different between arms, nor were any of the secondary endpoints of local control, progression free survival, and overall survival. Patients who received single fraction SBRT reported improved dyspnea and social functioning in follow up questionnaires.  This study concludes that single fraction is safe and effective, although one should note that efficacy was limited to secondary endpoints.

Reference (PubMed Link): Singh AK, Gomez-Suescun JA, Stephans KL, et al. One versus three fractions of stereotactic body radiation therapy for peripheral stage i to ii non-small cell lung cancer: A randomized, multi-institution, phase 2 trial. Int J Radiat Oncol Biol Phys 2019;105:752-759.

Key Institution: Multi-institutional/USA 
Keywords: Single fraction, SBRT, NSCLC 

This trial evaluated the use of SBRT for early stage lung cancer patients who were operable, whereas historically SBRT was reserved for medically inoperable patients. The primary endpoint was local control, and survival, adverse events, and the incidence of surgical salvage, as secondary endpoints.

With median follow up of 48.1 months, 26 of 33 enrolled patients were evaluable. Of those evaluable 23/26 were T1 and 3 were T2. The median FEV1 and DLCO were 72% (38-136) and 68% (22-96), respectively.

One patient had primary tumor recurrence; 4 year local control 96%. OS and DFS at 4 years was 56% and 57%, respectively. LRC at 4 years was 88% (3 regional failures) and DM rate was 12% (5 patients). Grade 3 AE rate 14%, no grade 4.

SBRT appears to have a high probability of tumor control, low morbidity, and little need for surgical salvage in patients with early-stage operable lung cancer.

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This paper is a NCDB analysis of early-stage NSCLC that shows improved 30-day mortality with SABR vs. surgery. The authors identified 76,623 patients who were treated with surgery or SABR for early-stage NSCLC (T1-T2a N0 M0) and compared their 30-day and 90-day post-treatment

Patients with SABR had significantly improved mortality at both 30-days and 90-days compared to patients who received surgery in both unmatched and propensity-matched analyses. Elder patients (>70 years) had greatest mortality benefit with SABR vs. surgery. Patients treated with pneumonectomy had worst absolute mortality as would be expected. These results strongly show that SABR may be safer than surgery especially in the peri-treatment period and for elderly patients, as we would intuitively expect. This is despite SABR patients typically being chosen because they are poor operative candidates, thus generally being frailer. This study has limitations as a retrospective NCDB analysis, with the cohorts not being perfectly matched, as shown in table 1 with nearly every pre-treatment treatment/site/stage/epidemiologic factor being significantly different between the surgery and SABR groups. Also, the authors limit the analysis to only T1-T2a patients and don’t include T2b N0 patients who are also generally strong candidates for both lobectomy and for SABR. In addition, there is no data on survival/mortality beyond the 90 day period; it would be interesting to see if any of the early mortality trends continued subsequently and if that also correlated with age. Still, despite these limitations, this paper is probably the largest and strongest to date showing that for older patients SABR may be strongly preferable to surgery to decrease risk of peri-treatment mortality. It is thus potentially practice-changing especially for older patients who are borderline surgical candidates, as physicians may be more likely to recommend SABR based on the results of this study.

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