Stereotactic body radiation therapy and 3-dimensional conformal radiotherapy for stage I non-small cell lung cancer: A pooled analysis of biological equivalent dose and local control.

PURPOSE To determine the relationship between tumor control probability (TCP) and biological effective dose (BED) for radiation therapy in medically inoperable stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS Forty-two studies on 3-dimensional conformal radiation therapy (3D-CRT) and SBRT for stage I NSCLC were reviewed for tumor control (TC), defined as crude local control ≥ 2 years, as a function of BED. For each dose-fractionation schedule, BED was calculated at isocenter using the linear quadratic (LQ) and universal survival curve (USC) models. A scatter plot of TC versus BED was generated and fitted to the standard TCP equation for both models. RESULTS A total of 2696 patients were included in this study (SBRT: 1640; 3D-CRT: 1056). Daily fraction size was 1.2-4 Gy (total dose: 48-102.9) with 3D-CRT and 6-26 (total dose: 20-66) with SBRT. Median BED was 118.6 Gy (range, 68.5-320.3) and 95.6 Gy (range, 46.1-178.1) for the LQ and USC models, respectively. According to the LQ model, BED to achieve 50% TC (TCD50) was 61 Gy (95% confidence interval, 50.2-71.1). TCP as a function of BED was sigmoidal, with TCP ≥ 90% achieved with BED ≥ 159 Gy and 124 Gy for the LQ and USC models, respectively. CONCLUSIONS Dose-escalation beyond a BED 159 by LQ model likely translates into clinically insignificant gain in TCP but may result in clinically significant toxicity. When delivered with SBRT, BED of 159 Gy corresponds to a total dose of 53 Gy in 3 fractions at the isocenter.

[1]  B. Slotman,et al.  Limited field irradiation in early stage (T1-2N0) non-small cell lung cancer. , 1996, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[2]  Y. Onodera,et al.  Steep dose-response relationship for stage I non-small-cell lung cancer using hypofractionated high-dose irradiation by real-time tumor-tracking radiotherapy. , 2008, International journal of radiation oncology, biology, physics.

[3]  W. Mühlnickel,et al.  Stereotactic, high single-dose irradiation of stage I non-small cell lung cancer (NSCLC) using four-dimensional CT scans for treatment planning. , 2008, Lung cancer.

[4]  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.

[5]  Y. Tamaki,et al.  Radical radiotherapy for medically inoperable non-small cell lung cancer in clinical stage I: a retrospective analysis of 149 patients. , 1997, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[6]  J. Petersen,et al.  Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer , 2005 .

[7]  I. Lax,et al.  The role of radiotherapy in treatment of stage I non-small cell lung cancer. , 2003, Lung cancer.

[8]  Yongshun Chen,et al.  Dose-individualized stereotactic body radiotherapy for T1-3N0 non-small cell lung cancer: long-term results and efficacy of adjuvant chemotherapy. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  L. Edwards,et al.  Factors associated with decisions to undergo surgery among patients with newly diagnosed early-stage lung cancer. , 2010, JAMA.

[10]  T. Araki,et al.  Stereotactic hypofractionated high‐dose irradiation for stage I nonsmall cell lung carcinoma , 2004, Cancer.

[11]  D. Heron,et al.  Stereotactic radiosurgery for the treatment of stage I non-small cell lung cancer in high-risk patients. , 2009, The Journal of thoracic and cardiovascular surgery.

[12]  P. Corcoran,et al.  Impact of revised stage classification of lung cancer on survival: a military experience. , 1999, Chest.

[13]  I. Chetty,et al.  Three-dimensional conformal radiation may deliver considerable dose of incidental nodal irradiation in patients with early stage node-negative non-small cell lung cancer when the tumor is large and centrally located. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  Yoshihiro Takai,et al.  A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  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.

[16]  M. Graham,et al.  Radiation therapy alone for stage I non-small cell lung cancer. , 1993, International journal of radiation oncology, biology, physics.

[17]  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.

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

[19]  Hiroki Shirato,et al.  STEREOTACTIC RADIATION THERAPY WORKSHOP Hypofractionated Stereotactic Radiotherapy (HypoFXSRT) for Stage I Non-small Cell Lung Cancer: Updated Results of 257 Patients in a Japanese Multi-institutional Study , 2007 .

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

[21]  Umberto Ricardi,et al.  Stereotactic body radiation therapy for early stage non-small cell lung cancer: results of a prospective trial. , 2010, Lung cancer.

[22]  E. Smit,et al.  Outcomes of risk-adapted fractionated stereotactic radiotherapy for stage I non-small-cell lung cancer. , 2008, International journal of radiation oncology, biology, physics.

[23]  B. Jeremic,et al.  Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer. , 1997, International journal of radiation oncology, biology, physics.

[24]  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.

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

[26]  R. V. van Klaveren,et al.  Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: clinical outcome. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[27]  R. Peschel,et al.  Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer. , 1987, International journal of radiation oncology, biology, physics.

[28]  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.

[29]  J. Birkmeyer,et al.  Outcomes in octogenarians undergoing high-risk cancer operation: a national study. , 2007, Journal of the American College of Surgeons.

[30]  E. Noordijk,et al.  Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[31]  S. Senan,et al.  Stage I nonsmall cell lung cancer in patients aged > or =75 years: outcomes after stereotactic radiotherapy. , 2010, Cancer.

[32]  Jie Liu,et al.  Involved-field radiotherapy is effective for patients 70 years old or more with early stage non-small cell lung cancer. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[33]  L. Dominioni,et al.  Stage I nonsmall cell lung carcinoma , 2000, Cancer.

[34]  Jan Nyman,et al.  Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of patients treated in the Nordic countries , 2006, Acta oncologica.

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

[36]  G. Sibley Radiotherapy for patients with medically inoperable stage I nonsmall cell lung carcinoma , 1998, Cancer.

[37]  Matthias Guckenberger,et al.  Dose-response relationship for image-guided stereotactic body radiotherapy of pulmonary tumors: relevance of 4D dose calculation. , 2009, International journal of radiation oncology, biology, physics.

[38]  Y. Ung,et al.  Accelerated hypofractionation for early-stage non-small-cell lung cancer. , 2002, International journal of radiation oncology, biology, physics.

[39]  James Ze Wang,et al.  Stereotactic body radiation therapy: a novel treatment modality , 2010, Nature Reviews Clinical Oncology.

[40]  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.

[41]  W. Curran,et al.  The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I non-small cell lung cancer. , 1990, International journal of radiation oncology, biology, physics.

[42]  S. Tung,et al.  Hypofractionated stereotactic radiotherapy for medically inoperable stage I non-small cell lung cancer--report on clinical outcome and dose to critical organs. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[43]  D. Heron,et al.  Stereotactic radiosurgery for the treatment of lung neoplasm: initial experience. , 2007, The Annals of thoracic surgery.

[44]  E. Noordijk,et al.  Local irradiation alone for peripheral stage I lung cancer: could we omit the elective regional nodal irradiation? , 1996, International journal of radiation oncology, biology, physics.

[45]  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.

[46]  Seong Soo Shin,et al.  Fractionated stereotactic body radiation therapy for medically inoperable stage I lung cancer adjacent to central large bronchus. , 2009, Lung cancer.

[47]  Lech Papiez,et al.  Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. , 2008, International journal of radiation oncology, biology, physics.

[48]  M. Brundage,et al.  Involved-field radiotherapy alone for early-stage non-small-cell lung cancer. , 2000, International journal of radiation oncology, biology, physics.

[49]  Quynh-Thu Le,et al.  Results of a Phase I Dose-Escalation Study Using Single-Fraction Stereotactic Radiotherapy for Lung Tumors , 2006, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[50]  M. Martel,et al.  Results following treatment to doses of 92.4 or 102.9 Gy on a phase I dose escalation study for non-small cell lung cancer. , 2004, Lung cancer.

[51]  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.

[52]  Ping Li,et al.  Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer. , 2006, International journal of radiation oncology, biology, physics.

[53]  Toshio Ohashi,et al.  Stereotactic body radiotherapy for primary lung cancer at a dose of 50 Gy total in five fractions to the periphery of the planning target volume calculated using a superposition algorithm. , 2009, International journal of radiation oncology, biology, physics.

[54]  Angelika Hoess,et al.  Stereotactic single‐dose radiotherapy (radiosurgery) of early stage nonsmall‐cell lung cancer (NSCLC) , 2007, Cancer.