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Purpose: Stereotactic body radiation therapy for tumors near the central airways implies high-grade toxic effects, as concluded from the HILUS trial. However, the small sample size and relatively few events limited the statistical power of the study. We therefore pooled data from the prospective HILUS trial with retrospective data from patients in the Nordic countries treated outside the prospective study to evaluate toxicity and risk factors for high-grade toxic effects., Methods and Materials: All patients were treated with 56 Gy in 8 fractions. Tumors within 2 cm of the trachea, the mainstem bronchi, the intermediate bronchus, or the lobar bronchi were included. The primary endpoint was toxicity, and the secondary endpoints were local control and overall survival. Clinical and dosimetric risk factors were analyzed for treatment-related fatal toxicity in univariable and multivariable Cox regression analyses., Results: Of 230 patients evaluated, grade 5 toxicity developed in 30 patients (13%), of whom 20 patients had fatal bronchopulmonary bleeding. The multivariable analysis revealed tumor compression of the tracheobronchial tree and maximum dose to the mainstem or intermediate bronchus as significant risk factors for grade 5 bleeding and grade 5 toxicity. The 3-year local control and overall survival rates were 84% (95% CI, 80%-90%) and 40% (95% CI, 34%-47%), respectively., Conclusions: Tumor compression of the tracheobronchial tree and high maximum dose to the mainstem or intermediate bronchus increase the risk of fatal toxicity after stereotactic body radiation therapy in 8 fractions for central lung tumors. Similar dose constraints should be applied to the intermediate bronchus as to the mainstem bronchi., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The bronchial tolerance to high doses of radiation is not fully understood. However, in the event of a radiological accident with unintended exposure of the central airways to high doses of radiation it would be important to be able to anticipate the clinical consequences given the magnitude of the absorbed dose to different parts of the bronchial tree. Stereotactic body radiation therapy (SBRT) is a radiation treatment technique involving a few large fractions of photon external-beam radiation delivered to a well-defined target in the body. Despite generally favourable results, with high local tumour control and low-toxicity profile, its utility for tumours located close to central thoracic structures has been questioned, considering reports of severe toxic symptoms such as haemoptysis (bleedings from the airways), bronchial necrosis, bronchial stenosis, fistulas and pneumonitis. In conjunction with patient- and tumour-related risk factors, recent studies have analysed the absorbed radiation dose to different thoracic structures of normal tissue to better understand their tolerance to these high doses per fraction. Although the specific mechanisms behind the toxicity are still partly unknown, dose to the proximal bronchial tree has been shown to correlate with high-grade radiation side effects. Still, there is no clear consensus on the tolerance dose of the different bronchial structures. Recent data indicate that a too high dose to a main bronchus may result in more severe clinical side effects as compared to a smaller sized bronchus. This review analyses the current knowledge on the clinical consequences of bronchial exposure to high dose hypofractionated radiation delivered with the SBRT technique, and the tolerance doses of the bronchi. It presents the current literature regarding types of high-grade clinical side effects, data on dose response and comments on other risk factors for high-grade toxic effects., (Creative Commons Attribution license.)

Background and Purpose: Stereotactic body radiotherapy (SBRT) for tumours ≥5 cm is poorly studied and its utility and feasibility is uncertain. We here report the Karolinska experience of SBRT in this setting., Material and Methods: All patients had a gross tumour volume (GTV) ≥70 cc, a prescribed physical dose of at least 40 Gy and received treatment between 1995-2012., Results: We included 164 patients with 175 tumours located in the thorax ( n  = 86), the liver ( n  = 27) and the abdomen ( n  = 62) and treated with a median prescribed dose (BED α/β 10Gy ) of 80 Gy (71.4-113). One- and 2- year local control rates were 82% and 61%. In multivariate analyses, minimum dose to the GTV and histological subtype were associated with local control. Renal cell carcinoma (RCC) histology showed the most favourable local control - 94% at 2 years for all histologies. Thirty-seven patients experienced grade 3-5 toxicity most likely related to SBRT. Seven of the ten patients with grade 5 toxicity, had a centrally located tumour in the thorax., Conclusion: SBRT of tumours >5 cm in diameter may be an option for peripherally located lung and abdominal tumours. Histological origin and tumour location should be considered before treatment.

Purpose : To evaluate the rate and dose response of brachial plexus toxicity post stereotactic body radiation therapy (SBRT) of apically situated lung lesions. Material/methods: We retrospectively identified all patients with apically located tumors, defined by the epicenter of the tumor being located superiorly to the aortic arch, and treated with SBRT between 2008 and 2013. Patients with a shorter follow-up than 6 months were excluded. Primary aim was to evaluate radiation-induced brachial plexopathy (RIBP). Dose to the plexus was assessed by a retrospective delineation of the brachial plexus on the CT used for treatment planning. Then, D max , D 0.1cc , D 1cc and D 3.0cc of the brachial plexus were collected from the dose-volume histograms (DVH) and recalculated to the biologically effective dose (BED) using α/β = 3 Gy. A normal tissue complication probability (NTCP) model, based on four different dose-volume parameters (BED 3,max , BED 3,0.1cc, BED 3,1.0cc, BED 3,3.0cc ) was fitted to the data. Results: Fifty-two patients with 56 apically located tumors were identified. Median prescription dose per fraction was 15 Gy (range 6-17) and median number of fractions was 3 (3-10). With a median follow-up of 30 months (6.1-72) seven patients experienced maximum grade 2 (scored 3 times) or 3 (scored 4 times) RIBP after a median of 8.7 months (range 4.0-31). Three patients had combined symptoms with pain, sensory and motor affection and four patients had isolated pain. Median BED 3,max for the patients experiencing RIBP was 381 Gy (range 30-524) versus BED 3,max of 34 Gy (range 0.10-483) for the patients without RIBP. The NTCP models showed a very high predictive ability (area under the receiver operating characteristic curve (AUC) 0.80-0.88). Conclusion: SBRT of apically located lung lesions may cause severe neurological symptoms; for a three-fraction treatment, we suggest that the maximum dose to the plexus should be kept ≤30 Gy (130 Gy BED 3 ).