A study by a team of researchers at the Karl Landsteiner University of Health Sciences in Austria (KL Krems) shows that higher radiation doses in lung cancer treatment carry no added risk of inflammation – and may improve survival.
The researchers found that that a higher-than-usual doses of radiation in the treatment of inoperable lung cancer can be safely combined with immunotherapy without increasing the risk of pneumonitis or severe lung inflammation. According to the researchers involved in the study, this is key finding of a recent study.
Patients who received 70 Gy (Gray*) of radiation – a dose above the conventional protocol – prior to treatment with the immune checkpoint inhibitor durvalumab (Imfinzi®; AstraZeneca) did not develop pneumonitis more frequently than those given a lower dose. At the same time, preliminary data suggest a significant survival benefit.
The findings, based on a retrospective evaluation of nearly 40 patients, suggest that more intensive radiotherapy may offer improved outcomes without compromising safety in selected cases.
Most common and deadliest forms of cancer
Lung cancer remains one of the most common and deadliest forms of cancer worldwide. For patients with inoperable stage III non-small cell lung cancer (NSCLC), the established standard of care is concurrent chemoradiotherapy (CCRT) followed by immunotherapy with durvalumab – particularly for tumors that express the PD-L1 protein, which enables cancer cells to evade the body’s immune system.
However, both radiotherapy and immunotherapy are known to carry a risk of inducing pneumonitis. As a result, total radiation doses have traditionally been limited to 60 Gy. Researchers at KL Krems set out to investigate whether higher doses – which could potentially lead to better tumour control – could be administered without increasing the risk of serious side effects.
Currently, there is no data on pneumonitis in patients receiving CCRT with an overall dose of 70 Gy compared with the standard protocol of 60 Gy ± 10% in this setting.[1]
Increased dosed without additional burden
“As part of a retrospective clinical study, we investigated whether increasing the radiation dose to 70 Gy would lead to a higher incidence of pneumonitis – and it did not,” noted Felix Schragel, MD, specialist in pulmonology at University Hospital Krems, a teaching and research centre of KL Krems. [1]
“In fact, there was a clear trend toward improved overall survival,” Schragel added.
Participating patients received either yje higher dose of 70 Gy (n = 29) or lower than 70 Gy total dose (n = 10) in 2 Gy fractions with an individually reduced dose.
Both groups had comparable baseline characteristics, allowing for a reliable and meaningful comparison. The incidence of pneumonitis was similar in both groups and consistent with data from previous studies. In addition, most cases were mild to moderate in severity.
Of the 39 participating patients, 15 (38.5%) developed pneumonitis with 10 out of 29 (34.5%) in the 70 Gy group and five out 10 (50%) in the < 70 Gy group.
However, the rate was actually lower in the 70 Gy group, at 34.5%, compared to 50% in the group that received the lower dose. Only one case of more severe pneumonitis (grade 3) was reported – and it occurred in the lower-dose group.
The survival data were particularly striking: in the high-dose (70 Gy) group, more than 93% of patients were still alive one year after treatment – and that figure remained virtually unchanged at the four-year mark.**
By contrast, the median survival in the lower-dose group was 31 months, and tumor progression was more frequent in this group.
Planning and safety
Radiation-induced lung damage was avoided thanks to careful and precise treatment planning. In both groups, the mean lung dose (MLD) was kept below the critical threshold of 20 Gy.
“As long as clinicians adhere to established safety limits – especially in regard to low-dose lung volumes – we don’t expect to see an increased rate of pneumonitis,” Schragel said.
“These results clearly show that administering a higher radiation dose to the tumor does not necessarily mean a higher risk of inflammatory side effects – provided the treatment is well planned,” Schragel added.
The study highlights the potential for more personalized treatment strategies in patients with unresectable stage III non-small cell lung cancer (NSCLC).
“For selected patients with stable lung function, intensified radiotherapy could significantly improve overall survival,” Schragel further noted.
“[] I’m particularly pleased that KL Krems is taking a leading role in this area – producing research with direct relevance for clinical practice,” Schragel concluded.
At the same time, the findings underline the importance of regularly re-evaluating established treatment thresholds in the light of evolving treatment approaches such as immunotherapy.
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Note:* Gy or Gray, the unit of absorbed radiation dose.
**The 70 Gy group showed a significant benefit in mortality (p = < 0.001). Overall survival (OS) differed significantly between groups (p =0.028).
Highlights of prescribing information
Durvalumab (Imfinzi®; AstraZeneca)[Prescribing Information]
Reference
[1] Schragel F, Matousek M, Resl C, Kreye G, Le NS, Errhalt P, Georg P, Hackner K. High radiation dose in chemoradiotherapy followed by immunotherapy with durvalumab in patients with stage III non-small cell lung cancer does not increase risk for pneumonitis. Strahlenther Onkol. 2025 Feb 13. doi: 10.1007/s00066-025-02369-0. Epub ahead of print. PMID: 39945842.
Featured image: Lungs.© 2019 – 2025 Robina Weermeijer. Used under the Unsplash License
DOI
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