H. Tekatli

Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with “Ultracentral” Non–Small Cell Lung Cancer

Introduction: We defined “ultracentral” lung tumors as centrally located non–small cell lung cancers with planning target volumes overlapping the trachea or main bronchi. Increased toxicity has been reported after both conventional and stereotactic radiotherapy for such lesions. We studied outcomes after 12 fractions of 5 Gy (BED10 = 90 Gy, heterogeneous dose distribution) to ultracentral tumors in patients unfit for surgery or conventional chemoradiotherapy. Methods: Clinical outcomes and dosimetric details were analyzed in 47 consecutive patients with single primary or recurrent ultracentral non–small cell lung cancer treated between 2010 and 2015. Those irradiated previously or with metastasis to sites other than the brain and adrenal glands were excluded. Treatments were delivered using volumetric modulated arc therapy. Results: The median age was 77.5 years, 49% of patients had a World Health Organization performance score of 2 or higher, and the median planning target volume was 104.5cm3 (range 17.7–508.5). At a median follow‐up of 29.3 months, median overall survival was 15.9 months, and 3‐year survival was 20.1%. No isolated local recurrences were observed. Grade 3 or higher toxicity was recorded in 38% of patients, with 21% scored as having a “possible” (n = 2) or “likely” (n = 8) treatment‐related death between 5.2 and 18.2 months after treatment. Fatal pulmonary hemorrhage was observed in 15% of patients. Conclusions: Unfit patients with ultracentral tumors who were treated using this scheme had a high local control and a median survival of 15.9 months. Despite manifestation of rates of a fatal lung bleeding comparable to those seen with conventional radiotherapy for endobronchial tumors, the overall rate of G5 toxicity is of potential concern. Additional work is needed to identify tumor and treatment factors related to hemorrhage.

Stereotactic ablative radiotherapy (SABR) for central lung tumors: Plan quality and long-term clinical outcomes.

BACKGROUND AND PURPOSE Central lung SABR is less established due to toxicity concerns. We describe plan quality and clinical outcomes for patients treated with VMAT SABR using 8×7.5Gy. MATERIALS AND METHODS We studied 80 consecutive patients with primary NSCLC and PTV ⩽2cm from the proximal bronchial tree (PBT), treated between 2008 and 2013. Dosimetric data were compared with institutional guidelines and study protocols, and long-term clinical outcomes were analyzed. RESULTS PTV V95% was 60Gy in 96% of patients. Dmax was ⩾60Gy in 40% of patients for PBT, 26.3% for aorta, 55% for heart, and 1.3% for trachea. Esophageal maximum Dmax was 58Gy. Mean lung V5Gy/V20Gy was 21/8%. 54 patients (68%) exceeded RTOG0813 Dmax for ⩾1 organ-at-risk (OAR), with 27 exceeding PBT Dmax. 5 of 78 patients (6.4%) with adequate follow-up information had grade 3 toxicity. Grade 4 toxicity was not observed. Treatment-related death was considered possible (n=3) or likely (n=3) in 6 patients (7.5%). With median follow-up of 47months, 3-year survival was 53%, compared with 57% for 252 peripheral tumors treated with 3/5-fractions SABR in the same period (p=0.369). CONCLUSIONS Although a substantial proportion of central SABR patients received ⩾60Gy to OARs, the 3-year survival was no different from peripheral SABR.

Use of Stereotactic Ablative Radiotherapy (SABR) in Non–Small Cell Lung Cancer Measuring More Than 5 cm

Introduction: Stereotactic ablative radiotherapy (SABR) is currently not the guideline‐recommended treatment for lung tumors measuring more than 5 cm. However, improvements in radiotherapy techniques have led to increasing use of SABR for larger tumors. Methods: We analyzed the clinical outcomes in patients with a primary or recurrent NSCLC measuring more than 5 cm and treated with five or eight fractions of SABR at our center. Patients who had prior thoracic radiotherapy were excluded. Results: A total of 63 consecutive patients with a median tumor diameter of 5.8 cm (range 5.1–10.4) were identified; 81% had T2N0 disease and 18% had T3N0 disease. The median Charlson comorbidity index was 2 (range 0–6). After a median follow‐up of 54.7 months, median survival was 28.3 months. Disease‐free survival at 2 years was 82.1%, and the local, regional, and distant control rates at 2 years were 95.8%, 93.7%, and 83.6%, respectively. An out‐of‐field distant recurrence at one or more sites was the most common pattern of failure (10%). Grade 3 or higher toxicity was recorded in 30% of patients, with radiation pneumonitis being the most common toxicity (19%). A likely (n = 4) or possible (n = 8) treatment‐related death was scored in 19% of patients. There was preexisting interstitial lung disease in eight patients (13%), with fatal toxicity developing in five of them (63%). Conclusions: Lung SABR in tumors larger than 5 cm resulted in high local control rates and acceptable survival outcomes in a patient population with appreciable comorbidity. Patients with interstitial lung disease should be considered a very high‐risk population for SABR.

Optimizing SABR delivery for synchronous multiple lung tumors using volumetric-modulated arc therapy

Abstract Background: Volumetric-modulated arc therapy (VMAT) delivery for stereotactic ablative radiotherapy (SABR) of multiple lung tumors allows for faster treatments. We report on clinical outcomes and describe a general approach for treatment planning. Material and methods: Patients undergoing multi iso-center VMAT-based SABR for ≥2 lung lesions between 2009 and 2014 were identified from the VU University Medical Center and London Health Sciences Centre. Patients were eligible if the start date of the SABR treatment for the different lesions was within a time range of 30 days. SABR was delivered using separate iso-centers for lesions at a substantial distance from each other. Tumors were either treated with a single fraction of 34 Gy, or using three risk-adapted dose-fractionation schemes, namely three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, depending on the tumor size and the location. Multivariable analysis was performed to assess factors predictive of clinical outcomes. Results: Of 84 patients (188 lesions) identified, 46% were treated for multiple metastases and 54% for multiple primary NSCLC. About 97% were treated for two or three lesions, and 56% had bilateral disease. After a median follow-up of 28 months, median overall survival (OS) for primary tumors was 27.6 months, and not reached for metastatic lesions (p = .028). Grade ≥3 toxicity was observed in 2% of patients. Multivariable analysis showed that grade 2 or higher radiation pneumonitis (n = 9) was best predicted by a total lung V35Gy of ≥6.5% (in 2Gy/fraction equivalent) (p = .007). Conclusion: Severe toxicity was uncommon following SABR using VMAT for up to three lung tumors. Further investigations of planning parameters are needed in patients presenting with more lesions.

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

PURPOSE To correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model. METHODS AND MATERIALS Patients 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 2 Gy 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. RESULTS Two-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 67 Gy EQD210 and D1cc of 42 Gy EQD210. No difference in overall survival was observed between patients with and without toxicity (p = 0.428). CONCLUSION As no grade 3-5 esophageal toxicity was observed in our cohort, a Dmax of 56 Gy EQD210 and a D5cc of 35.5 Gy 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.