Clinical outcome of hypofractionated breath-hold image-guided SABR of primary lung tumors and lung metastases

BackgroundStereotactic Ablative RadioTherapy (SABR) of lung tumors/metastases has been shown to be an effective treatment modality with low toxicity. Outcome and toxicity were retrospectively evaluated in a unique single-institution cohort treated with intensity-modulated image-guided breath-hold SABR (igSABR) without external immobilization. The dose–response relationship is analyzed based on Biologically Equivalent Dose (BED).Patients and methods50 lesions in 43 patients with primary NSCLC (n = 27) or lung-metastases of various primaries (n = 16) were consecutively treated with igSABR with Active-Breathing-Coordinator (ABC®) and repeat-breath-hold cone-beam-CT. After an initial dose-finding/-escalation period, 5x12 Gy for peripheral lesions and single doses of 5 Gy to varying dose levels for central lesions were applied. Overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC) and toxicity were analyzed.ResultsThe median BED2 was 83 Gy. 12 lesions were treated with a BED2 of <80 Gy, and 38 lesions with a BED2 of >80 Gy. Median follow-up was 15 months. Actuarial 1- and 2-year OS were 67% and 43%; respectively. Cause of death was non-disease-related in 27%. Actuarial 1- and 2-year PFS was 42% and 28%. Progression site was predominantly distant. Actuarial 1- and 2 year LC was 90% and 85%. LC showed a trend for a correlation to BED2 (p = 0.1167). Pneumonitis requiring conservative treatment occurred in 23%.ConclusionIntensity-modulated breath-hold igSABR results in high LC-rates and low toxicity in this unfavorable patient cohort with inoperable lung tumors or metastases. A BED2 of <80 Gy was associated with reduced local control.

[1]  H. Geinitz,et al.  Stereotactic hypofractionated radiotherapy in stage I (T1-2 N0 M0) non-small-cell lung cancer (NSCLC) , 2006, Acta oncologica.

[2]  M. Hiraoka,et al.  Prognostic factors in stereotactic body radiotherapy for non-small-cell lung cancer. , 2011, International journal of radiation oncology, biology, physics.

[3]  Matthias Guckenberger,et al.  kV Cone-Beam CT-Based IGRT , 2011, Strahlentherapie und Onkologie.

[4]  F. Lohr,et al.  Multiple breath-hold CBCT for online image guided radiotherapy of lung tumors: simulation with a dynamic phantom and first patient data. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[5]  Daniel W. Miller,et al.  Hypofractionated proton beam radiotherapy for stage I lung cancer. , 2004, Chest.

[6]  Matthias Guckenberger,et al.  Cone-beam CT based image-guidance for extracranial stereotactic radiotherapy of intrapulmonary tumors , 2006, Acta oncologica.

[7]  Steven H. Lin,et al.  Status of particle therapy for lung cancer , 2011, Acta oncologica.

[8]  P. Brown,et al.  Proton beam radiotherapy versus three-dimensional conformal stereotactic body radiotherapy in primary peripheral, early-stage non-small-cell lung carcinoma: a comparative dosimetric analysis. , 2009, International journal of radiation oncology, biology, physics.

[9]  L. Gaspar,et al.  Observation of a dose-control relationship for lung and liver tumors after stereotactic body radiation therapy. , 2009, International journal of radiation oncology, biology, physics.

[10]  L. Constine,et al.  Normal tissue toxicity after small field hypofractionated stereotactic body radiation , 2008, Radiation oncology.

[11]  Yuta Shibamoto,et al.  High‐dose proton therapy and carbon‐ion therapy for stage I nonsmall cell lung cancer , 2010, Cancer.

[12]  Lech Papiez,et al.  Stereotactic body radiation therapy for early-stage non-small-cell lung carcinoma: four-year results of a prospective phase II study. , 2009, International journal of radiation oncology, biology, physics.

[13]  M. Mix,et al.  Stereotactic ablative radiotherapy for small lung tumors with a moderate dose , 2012, Strahlentherapie und Onkologie.

[14]  Jan Nyman,et al.  Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors , 2006, Acta oncologica.

[16]  L. Kestin,et al.  Lung metastases treated with image-guided stereotactic body radiation therapy. , 2013, Clinical oncology (Royal College of Radiologists (Great Britain)).

[17]  MIN-JEONG KIM,et al.  Intensity-modulated stereotactic body radiotherapy for stage I non-small cell lung cancer , 2012, Oncology letters.

[18]  Joshua D. Lawson,et al.  Locoregional and distant failure following image-guided stereotactic body radiation for early-stage primary lung cancer. , 2011, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[19]  Joe Y. Chang,et al.  Stereotactic body radiation therapy in centrally and superiorly located stage I or isolated recurrent non-small-cell lung cancer. , 2008, International journal of radiation oncology, biology, physics.

[20]  Hypofractionated image-guided breath-hold SABR (Stereotactic Ablative Body Radiotherapy) of liver metastases – clinical results , 2012, Radiation oncology.

[21]  Barbara Dobler,et al.  Frameless Stereotactic Radiosurgery of a Solitary Liver Metastasis Using Active Breathing Control and Stereotactic Ultrasound , 2006, Strahlentherapie und Onkologie.

[22]  J. Sonke,et al.  A multinational pooled analysis of 434 cases of stage I non-small cell lung cancer (NSCLC) treated with volumetrically image-guided (VIGRT) stereotactic lung radiotherapy (SBRT): Results from the Elekta Collaborative Lung Research Group. , 2010 .

[23]  Jürgen Hesser,et al.  Accuracy of ultrasound-based (BAT) prostate-repositioning: a three-dimensional on-line fiducial-based assessment with cone-beam computed tomography. , 2008, International journal of radiation oncology, biology, physics.

[24]  R. Onimaru,et al.  Stereotactic body radiotherapy using gated radiotherapy with real-time tumor-tracking for stage I non-small cell lung cancer , 2013, Radiation oncology.

[25]  John Cho,et al.  Stereotactic body radiotherapy for medically inoperable lung cancer: prospective, single-center study of 108 consecutive patients. , 2012, International journal of radiation oncology, biology, physics.

[26]  J. Itami,et al.  Clinical outcomes of single‐fraction stereotactic radiation therapy of lung tumors , 2006, Cancer.

[27]  Hiroshi Honda,et al.  Clinical results of stereotactic body radiotherapy for Stage I small-cell lung cancer: a single institutional experience , 2010, Journal of radiation research.

[28]  J. Chang,et al.  Once-weekly, high-dose stereotactic body radiotherapy for lung cancer: 6-year analysis of 60 early-stage, 42 locally advanced, and 7 metastatic lung cancers. , 2008, International journal of radiation oncology, biology, physics.

[29]  P. Giraud,et al.  Dosimetric comparison of free-breathing and deep inspiration breath-hold radiotherapy for lung cancer , 2012, Strahlentherapie und Onkologie.

[30]  Hong Ye,et al.  Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Andrea Bezjak,et al.  Stereotactic body radiation therapy for inoperable early stage lung cancer. , 2010, JAMA.

[32]  U. Haedinger,et al.  Stereotactic radiotherapy of primary liver cancer and hepatic metastases , 2006, Acta oncologica.

[33]  J. Wong,et al.  The use of active breathing control (ABC) to reduce margin for breathing motion. , 1999, International journal of radiation oncology, biology, physics.

[34]  E. Smit,et al.  Stage I-II non-small-cell lung cancer treated using either stereotactic ablative radiotherapy (SABR) or lobectomy by video-assisted thoracoscopic surgery (VATS): outcomes of a propensity score-matched analysis. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[35]  Lech Papiez,et al.  Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  C. De Wagter,et al.  Lethal pneumonitis in a phase I study of chemotherapy and IMRT for NSCLC: the need to investigate the accuracy of dose computation. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[37]  Masahiro Hiraoka,et al.  Stereotactic body radiotherapy for oligometastatic lung tumors. , 2008, International journal of radiation oncology, biology, physics.

[38]  Jan Nyman,et al.  Radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy of non-small cell lung cancer: a dose- and volume-response analysis. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[39]  R K Ten Haken,et al.  Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: update of a phase I trial. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  Billy W Loo,et al.  Stereotactic ablative radiotherapy (SABR) for lung cancer: What does the future hold? , 2011, Journal of thoracic disease.

[41]  Masahiro Hiraoka,et al.  Clinical outcomes of a phase I/II study of 48 Gy of stereotactic body radiotherapy in 4 fractions for primary lung cancer using a stereotactic body frame. , 2005, International journal of radiation oncology, biology, physics.

[42]  Issam El Naqa,et al.  Lung STEREOTACTIC BODY RADIATION THERAPY FOR EARLY-STAGE NON – SMALL-CELL LUNG CANCER : THE PATTERN OF FAILURE IS DISTANT , 2010 .

[43]  Lech Papiez,et al.  Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: phase I study. , 2005, International journal of radiation oncology, biology, physics.

[44]  J. Sonke,et al.  A Collaborative Analysis of Stereotactic Lung Radiotherapy Outcomes for Early-Stage Non–Small-Cell Lung Cancer Using Daily Online Cone-Beam Computed Tomography Image-Guided Radiotherapy , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[45]  Marcel van Herk,et al.  Short-term and long-term reproducibility of lung tumor position using active breathing control (ABC). , 2006, International journal of radiation oncology, biology, physics.

[46]  M. Schell,et al.  Descriptive analysis of oligometastatic lesions treated with curative-intent stereotactic body radiotherapy. , 2008, International journal of radiation oncology, biology, physics.

[47]  Matthias Guckenberger,et al.  Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[48]  J. Wong,et al.  Long-term Results of Computed Tomography Guided Hypofractionated Stereotactic Radiotherapy for Stage I Non-small Cell Lung Cancers , 2008 .

[49]  John D Fenwick,et al.  A challenge to traditional radiation oncology. , 2004, International journal of radiation oncology, biology, physics.

[50]  Zhongxing Liao,et al.  Systemic review of the patterns of failure following stereotactic body radiation therapy in early-stage non-small-cell lung cancer: clinical implications. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[51]  P. Shueng,et al.  Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment - case report , 2010, BMC Cancer.

[52]  L. Gaspar,et al.  Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  J. Fowler,et al.  On cold spots in tumor subvolumes. , 2002, Medical physics.

[54]  Jeffrey Bradley,et al.  Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma. , 2005, International journal of radiation oncology, biology, physics.

[55]  Yasushi Nagata,et al.  Stereotactic radiotherapy of primary lung cancer and other targets: results of consultant meeting of the International Atomic Energy Agency. , 2011, International journal of radiation oncology, biology, physics.

[56]  B. Loo,et al.  Stereotactic ablative radiotherapy should be combined with a hypoxic cell radiosensitizer. , 2010, International journal of radiation oncology, biology, physics.