Article

Stereotactic body radiotherapy for central lung tumors.

Department of Therapeutic Radiology, Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut 06520, USA.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (impact factor: 4.55). 07/2012; 7(9):1394-9. DOI:10.1097/JTO.0b013e3182614bf3 pp.1394-9
Source: PubMed

ABSTRACT Patients with centrally located lung tumors have been reported to have a higher risk of toxicity when treated with stereotactic body radiotherapy (SBRT) compared with patients with peripheral tumors. The optimal SBRT fractionation schedule for treatment of central tumors is unknown. The primary purpose of this study was to assess toxicity in patients with central lesions treated with SBRT at our institution, the majority of whom were treated with four fractions.
Forty-seven patients with 51 central lesions, either primary lung cancer or lung metastases, were treated with SBRT at the Department of Therapeutic Radiology, Yale University School of Medicine/Yale Cancer Center from 2007 to 2011. The patients were treated with three to five fractions with the majority of patients receiving 50 Gy in four fractions of 12.5 Gy. Forty of the lesions were located within 2 cm of the proximal tracheobronchial tree whereas 11 were located within 2 cm of other mediastinal structures. Toxicity data were collected and analyzed according to pretreatment and tumor characteristics and dosimetric parameters. Lobar control data were compiled.
With a median follow-up of 11.3 months (range, 4.8-40.8), four patients experienced grade 3 dyspnea and one patient developed hemoptysis that contributed to respiratory failure and subsequent death. Grade 2 toxicity included fatigue (n = 3), dyspnea (n = 3), chest-wall pain (n = 1), and cough (n = 1). Patients with grade 3+ toxicity had larger maximum tumor diameters compared with those patients without grade 3+ toxicity (median diameter 4.3 cm versus 2.9 cm, p = 0.02). There were no detectable significant differences between the two groups with respect to baseline pulmonary function tests, distance to tracheobronchial tree, maximum point dose to the tracheobronchial tree, maximum dose to 5 cc of the tracheobronchial tree, mean lung dose, and volume of lung receiving 5 Gy, 10 Gy, and 20 Gy. There were two patients who experienced local recurrences. The median biological equivalent dose (linear quadratic formula, α/β = 10) for patients with local recurrence was 76 Gy compared with 112.5 Gy for patients without local recurrence (2-tailed t test, p = 0.04). The 2-year actuarial lobar local control for the entire cohort was 94%. The 2-year lobar local-control rate for patients receiving a biological equivalent dose of 100 Gy or more was 100% and for those receiving less than 100 Gy was 80% (log rank, p = 0.02).
SBRT for central lung tumors seems to be safe, although treatment of larger tumors does carry an increased risk of high-grade toxicity. Efforts to decrease the toxicity risk by decreasing the biologically equivalent dose resulted in increased local failure.

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    ABSTRACT: INTRODUCTION:: Although many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non-small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification. METHODS:: From April 2003 to December 2009, 70 histologically confirmed patients were treated with proton (n = 43) or carbon-ion (n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0. RESULTS:: The median follow-up period for living patients was 51 months (range, 24-103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients. CONCLUSION:: Particle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible.
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    ABSTRACT: Stereotactic body radiation therapy to centrally located or larger lung tumor results in higher toxicities. To over-come this challenge, we implemented a system that automatically selected and optimized noncoplanar beams. As a result, the dose conformality was signifi-cantly improved. Doses to heart, esophagus, trachea/ bronchus tree, spinal cord, and lungs were markedly reduced. The improved dosimetry would allow a planning target volume dose escalation from 50 to 68 Gy or higher to these tumors without exceeding critical organ dose limits. Purpose: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4p planning system. Methods and Materials: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7-to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4p plans, in which a column generation method was used to optimize the beam orientation and the flu-ence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were mini-mized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4p without violating dose limits set by the clinical plans. The deliverability of 4p plans was preliminarily tested. Results: Using 4p plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P .001), respectively, and R 50 was reduced by more than 50%. Lung V 20 , V 10 , and V 5 were reduced by 64%, 53%, and 32% (P .001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4p plans by 12% (PZ.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. Conclusions: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modu-lated arc therapy and static intensity modulated radiation therapy plans, the 4p plans yielded significantly and consistently improved tumor coverage and critical organ sparing. Given the known challenges in central structure dose constraints in stereotactic body radiation therapy to the lung, 4p planning may increase efficacy and reduce toxicity. Ó 2013 Elsevier Inc.
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    Article: 4π Noncoplanar Stereotactic Body Radiation Therapy for Centrally Located or Larger Lung Tumors.
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    ABSTRACT: PURPOSE: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4π planning system. METHODS AND MATERIALS: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4π plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4π without violating dose limits set by the clinical plans. The deliverability of 4π plans was preliminarily tested. RESULTS: Using 4π plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P≤.001), respectively, and R50 was reduced by more than 50%. Lung V20, V10, and V5 were reduced by 64%, 53%, and 32% (P≤.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4π plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. CONCLUSIONS: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4π plans yielded significantly and consistently improved tumor coverage and critical organ sparing. Given the known challenges in central structure dose constraints in stereotactic body radiation therapy to the lung, 4π planning may increase efficacy and reduce toxicity.
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Keywords

biological equivalent dose
 
biologically equivalent dose
 
central lung tumors
 
central tumors
 
Grade 2 toxicity
 
grade 3 dyspnea
 
grade 3+ toxicity
 
high-grade toxicity
 
linear quadratic formula
 
local recurrence
 
local recurrences
 
lung dose
 
lung tumors
 
maximum point dose
 
optimal SBRT fractionation schedule
 
peripheral tumors
 
proximal tracheobronchial tree
 
Therapeutic Radiology
 
tracheobronchial tree
 
tumor characteristics
 

Bryan P Rowe