M. Duijm

Dose and Volume of the Irradiated Main Bronchi and Related Side Effects in the Treatment of Central Lung Tumors With Stereotactic Radiotherapy.

High radiation dose to the main bronchi can result in stenosis, occlusion or fistula formation, and death. Only 8 articles have reported side effects to the main bronchi from stereotactic body radiation therapy (SBRT), mostly with only one symptomatic complication per article. Therefore, we calculated the dose to the bronchial structures, such as trachea; mainstem bronchi; intermediate bronchus; upper-, middle-, and lower-lobe bronchus; and the segmental bronchi in 134 patients with central tumors and calculated the normal tissue complication probability (NTCP) for each of these structures, with toxicity determination based upon computed tomography imaging. No side effects were found in the trachea, and only stenosis occurred in the main bronchus and bronchus intermedius. Higher grades of side effects, such as occlusion and atelectasis, were only seen in the upper-, middle-, and lower bronchi and the segmental bronchi. When 0.5cc of a segmental bronchi was irradiated to 50Gy in 5 fractions, it was about 50% likely to be occluded radiographically. For grade 1 radiographically evident side effects, the 50% risk level for a 5-fraction Dmax was 55Gy for mid-bronchi and 65Gy for mainstem bronchi. To assure the relationship between clinical toxicity and side effects to the bronchi, further investigation is needed.

Normal tissue complication probability (NTCP) modelling of pulmonary toxicity after stereotactic and hypo-fractionated radiotherapy for central lung tumors

PURPOSEnToxa0evaluate clinical pulmonary and radiographic bronchial toxicity after stereotactic ablative radiation therapy and hypofractionated radiation therapy for central lung tumors, and perform normal tissue complication probability modeling and multivariable analyses to identify predictors for toxicity.nnnMETHODS AND MATERIALSnA pooled analysis was performed of patients with a central lung tumor treated using ≤12 fractions at 2 centers between 2006 and 2015. Airways were manually contoured on planning computed tomography scans, and doses were recalculated to an equivalent dose of 2xa0Gy per fraction with an α/β ratio of 3. Grade ≥3 (≥G3) clinical pulmonary toxicity was evaluated by 2 or more physicians. Radiographic toxicity was defined as a stenosis or an occlusion with or without atelectasis using follow-up computed tomography scans. Logistic regression analyses were used for statistical analyses.nnnRESULTSnA total of 585 bronchial structures were studied in 195 patients who were mainly treated using 5 or 8 fractions (60%). Median patient survival was 27.9xa0months (95% confidence interval 22.3-33.6xa0months). Clinicalxa0≥G3 toxicity was observed in 24 patients (12%) and radiographic bronchial toxicity in 55 patients (28%), both mainly manifesting ≤12xa0months after treatment. All analyzed dosimetric parameters correlated with clinical and lobar bronchial radiographic toxicity, with V130Gy,EQD having the highest odds ratio. Normal tissue complication probability modeling showed a volume dependency for the development of both clinical and radiographic toxicity. On multivariate analyses, significant predictors forxa0≥G3 toxicity were a planning target volume overlapping the trachea or main stem bronchus (P = .005), chronic obstructive pulmonary disease (P = .034), and the total V130Gy,EQD (P = .012). Radiographic bronchial toxicity did not significantly correlate with clinical toxicity (P = .663).nnnCONCLUSIONSnWe identified patient and dosimetric factors associated with clinical and radiographic toxicity after high-dose radiation therapy for central lung tumors. Additional data from prospective studies are needed to validate these findings.

Esophagus toxicity after stereotactic and hypofractionated radiotherapy for central lung tumors: Normal tissue complication probability modeling

PURPOSEnTo correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model.nnnMETHODS AND MATERIALSnPatients with a central lung tumor from 2 centers, who underwent stereotactic or hypofractionated radiotherapy (≤12 fractions), were analyzed. Doses were recalculated to an equivalent dose of 2u202fGy with an α/β ratio of 10 (EQD210). The esophagus was manually delineated and DVH-parameters (Dmax,EQD2, D1cc,EQD2, D2cc,EQD2, D5cc,EQD2) were analyzed and used for NTCP modeling based on logistic regression analysis.nnnRESULTSnTwo-hundred-and-thirty-one patients with 252 tumors were eligible. No acute or late grade 3-5 esophageal toxicity was reported. Acute grade 1-2 esophagus toxicity was recorded in 38 patients (17%). All DVH-parameters were significantly higher in patients with toxicity. NTCP models showed a 50% probability of acute grade 1-2 toxicity at a Dmax of 67u202fGy EQD210 and D1cc of 42u202fGy EQD210. No difference in overall survival was observed between patients with and without toxicity (pu202f=u202f0.428).nnnCONCLUSIONnAs no grade 3-5 esophageal toxicity was observed in our cohort, a Dmax of 56u202fGy EQD210 and a D5cc of 35.5u202fGy EQD210 could be delivered without high risks of severe toxicity. The NTCP models of this study might be used as practical guidelines for the treatment of central lung tumors with stereotactic radiotherapy.

Stereotactic body radiotherapy for oligometastatic soft tissue sarcoma

BackgroundStereotactic body radiotherapy (SBRT) is emerging as a novel treatment option in metastatic soft tissue sarcoma (STS). The aim of our study was to evaluate the effectiveness of exclusive SBRT on disease control and survival in oligometastatic (≤u20093 synchronous lesions) STS.Materials and methodsIn total, 16 consecutive patients, accounting for 26 metastases (including 21 lung and 5 lymph node or soft tissue metastases), were treated at our institution with SBRT. Patient- and treatment-related characteristics were collected. Local control (LC), overall survival (OS), distant metastases-free survival (DMFS), and time to initiation of chemotherapy or best supportive care (corrected disease-free survival, cDFS) were assessed.ResultsFour-year OS was 54% and median OS was 69xa0months [95% confidence interval (CI) 20–118xa0months]. LC of 26 lesions at 4xa0years was 78%. Median DMFS and cDFS were 17 (95% CI 5–30xa0months) and 28xa0months (95% CI 5–52xa0months), respectively. Disease-free interval <u200924xa0months from primary tumor treatment to first metastasis was the only predictor of reduced LC, cDFS, and OS (pu2009=u20090.022, 0.023, and 0.028, respectively). No acute or chronic grade ≥u20093 toxicity was observed. Median follow-up was 36xa0months (IQR 18–71xa0months).ConclusionsIn patients with oligometastatic STS, SBRT yields satisfying local control with minimal toxicity. Median OS was 69xa0months. Repeated SBRT may be considered to extend disease-free and systemic therapy-free interval. Increased time from primary tumor to first metastasis identifies patients with potentially greater benefit from SBRT.

Local Reirradiation of Recurrent Non-small Cell Lung Carcinoma Resulting in Long Disease-free Survival, Although in the Presence of Osteonecrosis

High-dose reirradiation of the thorax can be offered to patients with only local disease progression of non-small-cell lung cancer (NSCLC) resulting in promising disease-free-survival. However, much is still unknown about related side-effects and occasionally an uncommon presentation can be caused by reirradiation. In this case report, we present a patient with a 3.5-year progression-free survival, although in the presence of a late, unexpected toxicity. A dosimetric analysis was performed to investigate the possibility of radiation-induced toxicity.