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Phase 2 trial of high-dose thoracic reirradiation shows 30-month median OS for recurrent lung cancer

Phase 2 trial of high-dose thoracic reirradiation shows 30-month median OS for recurrent lung cancer
Photo by CDC / Unsplash
Key Takeaway
Consider phase 2 data on high-dose reirradiation for thoracic recurrences as preliminary, single-arm evidence.

This prospective phase 2 clinical trial evaluated high-dose thoracic reirradiation in 60 analyzed patients with recurrent lung cancer in the thorax, specifically tumors located <5 cm from the 50 Gy EQD isodose line of previous radiation therapy. The intervention involved reirradiation to ≥45 Gy EQD using image-guided intensity modulated radiation therapy or volumetric modulated arc therapy, delivered via conventional fractionation (63% of patients, median dose 53 Gy) or stereotactic body radiation treatment (37%, median dose 77 Gy). No comparator group was included.

The primary outcome was median overall survival (OS), which was 30.1 months, exceeding the study's 12-month goal. Median local control (LC) was 28.2 months, and median disease-free survival (DFS) was 13.6 months. Statistical measures like p-values or confidence intervals were not reported for these outcomes.

Regarding safety, grade 3 toxicities occurred in 12 patients (20%), with pneumonitis being the most common (12%). No grade 4 or 5 toxicities were registered, indicating a low-toxicity profile. Discontinuation rates were not reported.

Key limitations include the single-arm, non-randomized phase 2 design with no comparator, a limited sample size of 60 analyzed patients, and the absence of reported statistical confidence intervals. The study design shows association, not causation. Practice relevance is not reported, and these findings should be interpreted as preliminary evidence requiring validation in larger, controlled studies before influencing clinical standards.

Study Details

Study typePhase2
Sample sizen = 64
EvidenceLevel 3
Follow-up12.0 mo
PublishedApr 2026
View Original Abstract ↓
PURPOSE: Locoregional failures after (chemo)radiation therapy for primary lung cancer account for 30% of relapses. Reirradiation in this setting is challenging. To evaluate the outcome after thoracic reirradiation with radical doses, a prospective phase 2 trial was conducted for marginal or in-field recurrences of lung cancer. METHODS AND MATERIALS: The goal of this study was to treat recurrent lung cancer with high-dose (chemo)radiation therapy to reach a median overall survival (OS) of 12 months. Patients with recurrent lung cancer in the thorax (tumor <5 cm from 50 Gy Equivalent Dose of 2 Gy per fraction [EQD] isodose line of previous radiation therapy) were reirradiated with ≥45 Gy EQD The secondary endpoints were local control (LC), disease-free survival (DFS), and toxicity. RESULTS: From 2018 to 2022, 64 patients were included, of whom 60 were analyzed. The median dose of the first radiation therapy course was 68 Gy EQD. All patients were reirradiated using image guided intensity modulated radiation therapy or volumetric modulated arc therapy: 38 patients (63%) using conventional fractionated radiation therapy (median dose 53 Gy) and 22 (37%) using stereotactic body radiation treatment (median dose 77 Gy). Median reirradiation planning target volume (PTV) was 106 cc. In 50 patients, the current PTV overlapped with the previous PTV. After a median follow-up of 26.5 months, median OS was 30.1 months, LC was 28.2 months, and DFS was 13.6 months. No grade 4-5 toxicities were registered. Grade 3 toxicities occurred in 12 patients (20%); the most common was pneumonitis (12%). CONCLUSIONS: This trial showed that high-dose thoracic reirradiation for recurrent lung cancer is effective and achieved a good OS higher than our null hypothesis. It resulted in good LC and DFS with low toxicity.
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