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• W2080765629 abstract "An increasing body of experience suggests that oligometastasis represents a minimal metastatic state with the potential for cure or prolonged survival in selected patients treated with radical local therapy to all identified sites of disease. The main clinical scenarios managed by thoracic oncology specialists are pulmonary oligometastases from primary malignancies of other anatomic sites and primary lung cancer with oligometastases to lung or other organs. Surgery has been a mainstay of treatment in these situations, with remarkably favorable outcomes following pulmonary metastasectomy in well-selected patient cohorts. As with early stage lung cancer in patients who are medically inoperable, stereotactic ablative radiotherapy is emerging as a prominent local treatment option for oligometastatic disease. We review the role and clinical experience of stereotactic ablative radiotherapy for pulmonary oligometastases and oligometastatic lung cancer. An increasing body of experience suggests that oligometastasis represents a minimal metastatic state with the potential for cure or prolonged survival in selected patients treated with radical local therapy to all identified sites of disease. The main clinical scenarios managed by thoracic oncology specialists are pulmonary oligometastases from primary malignancies of other anatomic sites and primary lung cancer with oligometastases to lung or other organs. Surgery has been a mainstay of treatment in these situations, with remarkably favorable outcomes following pulmonary metastasectomy in well-selected patient cohorts. As with early stage lung cancer in patients who are medically inoperable, stereotactic ablative radiotherapy is emerging as a prominent local treatment option for oligometastatic disease. We review the role and clinical experience of stereotactic ablative radiotherapy for pulmonary oligometastases and oligometastatic lung cancer. Metastatic disease in solid malignancies has historically been considered incurable, and the role of local therapies including radiation therapy has primarily been palliative. Though metastases are generally widely disseminated, a minimal metastatic state, dubbed oligometastasis,1Hellman S Weichselbaum RR Oligometastases.J Clin Oncol. 1995; 13: 8-10Crossref PubMed Google Scholar,2Weichselbaum RR Hellman S Oligometastases revisited.Nat Rev Clin Oncol. 2011; 8: 378-382Crossref PubMed Scopus (635) Google Scholar has been recognized, with a distinct natural history and a prognosis intermediate between that of localized and widely metastatic disease.1Hellman S Weichselbaum RR Oligometastases.J Clin Oncol. 1995; 13: 8-10Crossref PubMed Google Scholar, 2Weichselbaum RR Hellman S Oligometastases revisited.Nat Rev Clin Oncol. 2011; 8: 378-382Crossref PubMed Scopus (635) Google Scholar, 3Milano MT Katz AW Zhang H Okunieff P Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study.Int J Radiat Oncol Biol Phys. 2012; 83: 878-886Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar, 4Lo SS Moffatt-Bruce SD Dawson LA et al.The role of local therapy in the management of lung and liver oligometastases.Nat Rev Clin Oncol. 2011; 8: 405-416Crossref PubMed Scopus (99) Google Scholar, 5Milano MT Katz AW Muhs AG et al.A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions.Cancer. 2008; 112: 650-658Crossref PubMed Scopus (209) Google Scholar, 6Corbin KS Hellman S Weichselbaum RR Extracranial oligometastases: a subset of metastases curable with stereotactic radiotherapy.J Clin Oncol. 2013; 31: 1384-1390Crossref PubMed Scopus (155) Google Scholar Oligometastasis may be loosely defined clinically as a limited number of metastatic lesions in a limited number of organs, generally identified by imaging, suggesting the potential benefit of radical local therapies. This definition has evolved with advances in diagnostic tools and systemic and local treatments. Improved imaging, such as with whole body fluorodeoxyglucose positron emission tomography (PET), has increased the likelihood of detecting limited metastasis. Furthermore, it is thought that the improved effectiveness of systemic therapy for occult microscopic disease, such as with individualized targeted therapy, may increase the chance of cure following ablation of limited imaging-detected metastases. Aggressive local treatment, with the goal of ablating all known sites of disease, is an emerging treatment strategy for oligometastatic disease. However, determining the advantages or superiority of this approach compared to palliative systemic therapy or best supportive care is challenging because of the predominantly retrospective nature of existing data, which has raised substantial concerns for selection bias (performance status, disease-free interval, small metastatic burden) despite the use of techniques such as propensity score analyses. The ability to predict rapidly versus slowly progressive disease7Lussier YA Khodarev NN Regan K et al.Oligo- and polymetastatic progression in lung metastasis(es) patients is associated with specific microRNAs.PLoS One. 2012; 7: e50141Crossref PubMed Scopus (158) Google Scholar would be of major importance for the design of customized therapeutic strategies and for prospective clinical trials.5Milano MT Katz AW Muhs AG et al.A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions.Cancer. 2008; 112: 650-658Crossref PubMed Scopus (209) Google Scholar,8Milano MT Katz AW Okunieff P Patterns of recurrence after curative-intent radiation for oligometastases confined to one organ.Am J Clin Oncol. 2010; 33: 157-163PubMed Google Scholar Perhaps the best evidence for a local ablative approach for oligometastatic disease comes from treatment, most commonly surgery, of lung or liver oligometastases from colorectal cancer, performed sequentially following systemic treatment.9Cunningham D Atkin W Lenz HJ et al.Colorectal cancer.Lancet. 2010; 375: 1030-1047Abstract Full Text Full Text PDF PubMed Scopus (1267) Google Scholar This approach has since been extended to other cancer types. The two clinical scenarios most commonly treated by thoracic oncology specialists are pulmonary oligometastases from non-lung primary malignancies and primary lung cancer with or without oligometastases to the lung. Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy, is a rapidly emerging technique for the treatment of oligometastatic disease. SABR's role in the treatment of stage I lung cancer in patients is well established for inoperable patients,10Timmerman R Paulus R Galvin J et al.Stereotactic body radiation therapy for inoperable early stage lung cancer.JAMA. 2010; 303: 1070-1076Crossref PubMed Scopus (1938) Google Scholar while for patients who can tolerate surgery, lobectomy is the standard of care. For a third category of patients, who are considered at high risk for complications from a lobectomy but who might tolerate sublobar resections or other invasive procedures such as SABR or radiofrequency ablation, there is a lack of consensus regarding appropriate treatment, and, as with the comparison between lobectomy and SABR, this issue has only been explored retrospectively.11Crabtree T Puri V Timmerman R et al.Treatment of stage I lung cancer in high-risk and inoperable patients: comparison of prospective clinical trials using stereotactic body radiotherapy (RTOG 0236), sublobar resection (ACOSOG Z4032), and radiofrequency ablation (ACOSOG Z4033).J Thorac Cardiovasc Surg. 2013; 145: 692-699Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar The attractiveness of SABR in oligometastatic disease is due to its feasibility in an ambulatory setting, low side-effect profile, and efficacy.12Rusthoven KE Kavanagh BD Burri SH et al.Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases.J Clin Oncol. 2009; 27: 1579-1584Crossref PubMed Scopus (345) Google Scholar,13Rusthoven KE Kavanagh BD Cardenes H et al.Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases.J Clin Oncol. 2009; 27: 1572-1578Crossref PubMed Scopus (886) Google Scholar SABR may be performed sequentially with systemic therapy and is delivered in a small number of fractions (usually ⩽5), varying in size from 5 to more than 20 Gy each.14Chang HJ Ko HL Lee CY et al.Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using tomotherapy.Radiat Oncol. 2012; 7: 222Crossref PubMed Scopus (13) Google Scholar, 15Gomez DR Niibe Y Chang JY Oligometastatic disease at presentation or recurrence for nonsmall cell lung cancer.Pulm Med. 2012; 2012: 396592Crossref PubMed Scopus (18) Google Scholar, 16Oh D Ahn YC Seo JM et al.Potentially curative stereotactic body radiation therapy (SBRT) for single or oligometastasis to the lung.Acta Oncol. 2012; 51: 596-602Crossref PubMed Scopus (44) Google Scholar, 17Lopez Guerra JL Gomez D Zhuang Y et al.Prognostic impact of radiation therapy to the primary tumor in patients with non-small cell lung cancer and oligometastasis at diagnosis.Int J Radiat Oncol Biol Phys. 2012; 84: e61-e67Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar, 18Norihisa Y Nagata Y Takayama K et al.Stereotactic body radiotherapy for oligometastatic lung tumors.Int J Radiat Oncol Biol Phys. 2008; 72: 398-403Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar Here, we review the use of SABR for the treatment of pulmonary oligometastases and oligometastatic lung cancer. In 1997, the “International Registry on Lung Metastases,” a comprehensive research network among 18 major European and North American thoracic surgery departments, reported the results of 5206 lung metastasectomies, with 4572 (88%) complete resections. The primary tumor was epithelial in 2260, sarcoma in 2173, germ cell in 363, and melanoma in 328 patients.19Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. The International Registry of Lung Metastases.J Thorac Cardiovasc Surg. 1997; 113: 37-49Abstract Full Text Full Text PDF PubMed Scopus (1307) Google Scholar The actuarial survival after complete resection was 36% at 5 years, 26% at 10 years, and 22% at 15 years (median survival: 35 months); the corresponding values for incomplete resection were 13% at 5 years and 7% at 10 years (median survival: 15 months). Among complete resections, the 5-year survival was 33% for patients with a disease-free interval (DFI: time between initial diagnosis and onset of lung metastatic disease) below 11 months and 45% in patients with a DFI longer than 36 months; moreover, 5-year survival was superior for patients with single lesions (43% vs. 27%). These findings suggested a potentially curative role for surgery in a subset of metastatic patients, such as those with a completely resected single lesion (R0) and extended DFI. A recent large single-institution series confirmed these factors as prognostic,20Casiraghi M De Pas T Maisonneuve P et al.A 10-year single-center experience on 708 lung metastasectomies: the evidence of the “international registry of lung metastases”.J Thorac Oncol. 2011; 6: 1373-1378Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar with a survival projection at 2 and 5 years after complete resection (achievable in 85% of patients) of 74% and 46%, respectively. As a result of these findings, internationally accepted selection criteria for lung metastastectomy are good performance status, absence of extra-pulmonary metastases, control of the primary tumor, possibility of complete resection, and adequate respiratory function.21Kaifi JT Gusani NJ Deshaies I et al.Indications and approach to surgical resection of lung metastases.J Surg Oncol. 2010; 102: 187-195Crossref PubMed Scopus (71) Google Scholar All comprehensive series reported thus far comprise multiple primary tumors (e.g., epithelial, mesenchymal, germ cell tumors, and melanoma) and, among different epithelial tumors, histology has not been shown to be a significant prognostic factor. That being said, there are several reports from smaller series describing the results of surgical metastasectomy for colorectal cancer metastases. In a recent systematic review, Schlijper et al.22Schlijper RC Grutters JP Houben R et al.What to choose as radical local treatment for lung metastases from colo-rectal cancer: surgery or radiofrequency ablation?.Cancer Treat Rev. 2014; 40: 60-67Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar included 23 surgical reports, selected by a minimum follow-up of 24 months and a minimum of 50 patients, without regard to previous therapies, four of which were prospective studies. In this report, 2- and 5-year survival for metastasectomy ranged from 64% to 88% and 29% to 71.2%, respectively.22Schlijper RC Grutters JP Houben R et al.What to choose as radical local treatment for lung metastases from colo-rectal cancer: surgery or radiofrequency ablation?.Cancer Treat Rev. 2014; 40: 60-67Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar SABR is an ideal modality for treating pulmonary metastases with the goal of achieving high rates of tumor control with minimal morbidity, noninvasively (Fig. 1). The use of SABR in treating metastatic pulmonary nodules was a natural extension of its established role in the treatment for early stage non–small-cell lung cancers (NSCLC) not amenable to surgical resection. In oligometastatic disease, pulmonary lesions treated with SABR have a 1-year local control rate of 70% to 95%12Rusthoven KE Kavanagh BD Burri SH et al.Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases.J Clin Oncol. 2009; 27: 1579-1584Crossref PubMed Scopus (345) Google Scholar,18Norihisa Y Nagata Y Takayama K et al.Stereotactic body radiotherapy for oligometastatic lung tumors.Int J Radiat Oncol Biol Phys. 2008; 72: 398-403Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar,23Ricardi U Filippi AR Guarneri A et al.Stereotactic body radiation therapy for lung metastases.Lung Cancer. 2012; 75: 77-81Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 24Wulf J Haedinger U Oppitz U Thiele W Mueller G Flentje M Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: a noninvasive treatment approach in medically inoperable patients.Int J Radiat Oncol Biol Phys. 2004; 60: 186-196Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar, 25Brown WT Wu X Fowler JF et al.Lung metastases treated by CyberKnife image-guided robotic stereotactic radiosurgery at 41 months.South Med J. 2008; 101: 376-382Crossref PubMed Scopus (45) Google Scholar, 26Yoon SM Choi EK Lee SW et al.Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors.Acta Oncol. 2006; 45: 1108-1114Crossref PubMed Scopus (36) Google Scholar, 27Onimaru R Shirato H Shimizu S et al.Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers.Int J Radiat Oncol Biol Phys. 2003; 56: 126-135Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar, 28Okunieff P Petersen AL Philip A et al.Stereotactic Body Radiation Therapy (SBRT) for lung metastases.Acta Oncol. 2006; 45: 808-817Crossref PubMed Scopus (177) Google Scholar; a more limited number of studies, reporting single-fraction schedules, showed similar local control rates, especially for smaller tumors.29Filippi AR Badellino S Guarneri A et al.Outcomes of single fraction stereotactic ablative radiotherapy for lung metastases.Technol Cancer Res Treat. 2014; 13: 37-45PubMed Google Scholar, 30Hof H Hoess A Oetzel D Debus J Herfarth K Stereotactic single-dose radiotherapy of lung metastases.Strahlenther Onkol. 2007; 183: 673-678Crossref PubMed Scopus (76) Google Scholar, 31Osti MF Carnevale A Valeriani M et al.Clinical outcomes of single dose stereotactic radiotherapy for lung metastases.Clin Lung Cancer. 2013; 14: 699-703Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar All published series included a broad spectrum of different primary tumors, with the most represented histological subtypes being colorectal and lung cancer. Table 1 summarizes the results of clinical trials published over the last 10 years. The predominant clinical presentation was a single lung metastasis, with more limited reports of patients with two to five pulmonary nodules. Siva et al.32Siva S MacManus M Ball D Stereotactic radiotherapy for pulmonary oligometastases: a systematic review.J Thorac Oncol. 2010; 5: 1091-1099Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar reviewed several studies on SABR for lung metastases, with a total of 488 patients treated with a wide range of technical approaches and different dose-fractionation schedules, and demonstrated a 2-year weighted overall survival of approximately 50%. Furthermore, in a prospective pilot study on oligometastatic patients (<5 lesions), survival at 3 years was around 30% and at 5 years did not exceed 25%.5Milano MT Katz AW Muhs AG et al.A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions.Cancer. 2008; 112: 650-658Crossref PubMed Scopus (209) Google ScholarTABLE 1Clinical Trials of Stereotactic Ablative Radiotherapy for Pulmonary Oligometastatic Disease ReferenceNo. of PatientsNo. of TargetsRadiation DoseMedian Follow-Up (Months)OutcomesFractionated/Single Fraction SABR Onimaru et al.27Onimaru R Shirato H Shimizu S et al.Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers.Int J Radiat Oncol Biol Phys. 2003; 56: 126-135Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar203248 Gy/8 fx, 60 Gy/8 fx1848% 2-yr OS, 69.6% 3-yr LC for 48 Gy, 100% 3-yr LC for 60 Gy Yoon et al.26Yoon SM Choi EK Lee SW et al.Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors.Acta Oncol. 2006; 45: 1108-1114Crossref PubMed Scopus (36) Google Scholar538030 Gy/3 fx, 40 Gy/4 fx, 48 Gy/4 fx1470% LC for 30 Gy, 77% for 40 Gy, 100% LC for 48 Gy, 51% all 2-yr OS Okunieff et al.28Okunieff P Petersen AL Philip A et al.Stereotactic Body Radiation Therapy (SBRT) for lung metastases.Acta Oncol. 2006; 45: 808-817Crossref PubMed Scopus (177) Google Scholar5012550 Gy/10 fx, 48 Gy/6 fx, 57 Gy/3 fx18.791% 3-yr LC, 50% 2-yr OS Norihisa et al.18Norihisa Y Nagata Y Takayama K et al.Stereotactic body radiotherapy for oligometastatic lung tumors.Int J Radiat Oncol Biol Phys. 2008; 72: 398-403Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar344348 Gy/4 fx, 60 Gy/5 fx, at isocenter2790% 2-yr LC, 84% 2-yr OS Brown et al.25Brown WT Wu X Fowler JF et al.Lung metastases treated by CyberKnife image-guided robotic stereotactic radiosurgery at 41 months.South Med J. 2008; 101: 376-382Crossref PubMed Scopus (45) Google Scholar35695 Gy/1 fx to 60 Gy/4 fx1877% crude LC, 72.5% 2-yr OS Rusthoven et al.12Rusthoven KE Kavanagh BD Burri SH et al.Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases.J Clin Oncol. 2009; 27: 1579-1584Crossref PubMed Scopus (345) Google Scholar386360 Gy/3 fx at 80%15.496% 2-yr LC, 39% 2-yr OS Wulf et al.24Wulf J Haedinger U Oppitz U Thiele W Mueller G Flentje M Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: a noninvasive treatment approach in medically inoperable patients.Int J Radiat Oncol Biol Phys. 2004; 60: 186-196Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar415130 Gy/3 fx, 36 Gy/3 fx, 26 Gy/1 fx at 100%1380% 1-yr LC, 33% 2-yr OS Ricardi et al.23Ricardi U Filippi AR Guarneri A et al.Stereotactic body radiation therapy for lung metastases.Lung Cancer. 2012; 75: 77-81Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar617745 Gy/3 fx, 26 Gy/1 fx at 80%20.489% 2-yr LC, 66.5% 2-yr OSSingle Fraction SABR Only Hof et al.30Hof H Hoess A Oetzel D Debus J Herfarth K Stereotactic single-dose radiotherapy of lung metastases.Strahlenther Onkol. 2007; 183: 673-678Crossref PubMed Scopus (76) Google Scholar617112 to 30 Gy at isocenter1465.1% 2-yr OS Filippi et al.29Filippi AR Badellino S Guarneri A et al.Outcomes of single fraction stereotactic ablative radiotherapy for lung metastases.Technol Cancer Res Treat. 2014; 13: 37-45PubMed Google Scholar679026 Gy at 80%2488.1% 2-yr LC, 70.5% 2-yr OS Open table in a new tab Few consistent prognostic factors have emerged from various studies to guide appropriate patient selection for the treatment of oligometastatic pulmonary tumors. In two sequential reports by Milano et al.3Milano MT Katz AW Zhang H Okunieff P Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study.Int J Radiat Oncol Biol Phys. 2012; 83: 878-886Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar,5Milano MT Katz AW Muhs AG et al.A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions.Cancer. 2008; 112: 650-658Crossref PubMed Scopus (209) Google Scholar that included oligometastatic patients with less than five lesions in various organs including lung, the subgroup of breast cancer patients experienced superior rates of survival,3Milano MT Katz AW Zhang H Okunieff P Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study.Int J Radiat Oncol Biol Phys. 2012; 83: 878-886Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar while among non-breast epithelial subtypes, no significant differences were recorded. DFI (here defined as the interval between the initial diagnosis and the start of a local therapy for lung lesions) appears to have an impact for SABR, but results are unclear. Norihisa et al.18Norihisa Y Nagata Y Takayama K et al.Stereotactic body radiotherapy for oligometastatic lung tumors.Int J Radiat Oncol Biol Phys. 2008; 72: 398-403Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar found that DFI longer than 3 years was associated with better overall survival, and Filippi et al.29Filippi AR Badellino S Guarneri A et al.Outcomes of single fraction stereotactic ablative radiotherapy for lung metastases.Technol Cancer Res Treat. 2014; 13: 37-45PubMed Google Scholar reported that patients with a DFI longer than 2 years had better cancer-specific survival, on both univariate and multivariate analyses. Conversely, other studies failed to show a survival difference according to DFI.23Ricardi U Filippi AR Guarneri A et al.Stereotactic body radiation therapy for lung metastases.Lung Cancer. 2012; 75: 77-81Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar,24Wulf J Haedinger U Oppitz U Thiele W Mueller G Flentje M Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: a noninvasive treatment approach in medically inoperable patients.Int J Radiat Oncol Biol Phys. 2004; 60: 186-196Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar Tumor volume appears to be prognostic, with better outcomes in smaller tumors (<3.3 cc for gross tumor volume).23Ricardi U Filippi AR Guarneri A et al.Stereotactic body radiation therapy for lung metastases.Lung Cancer. 2012; 75: 77-81Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar Many patients included in these retrospective series, especially those with more than two pulmonary nodules, also received systemic therapy, either prior to or immediately after SABR, or at the time of a second progression. Few have been treated with further local therapies (including a second SABR) for oligometastatic recurrence or progression and it is difficult to estimate the contribution of these factors on survival. Reported 1- or 2-year progression-free survival (PFS) rates following SABR are highly variable, ranging from 25% to 70% and reflect the intrinsic heterogeneity of this patient population.23Ricardi U Filippi AR Guarneri A et al.Stereotactic body radiation therapy for lung metastases.Lung Cancer. 2012; 75: 77-81Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 24Wulf J Haedinger U Oppitz U Thiele W Mueller G Flentje M Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: a noninvasive treatment approach in medically inoperable patients.Int J Radiat Oncol Biol Phys. 2004; 60: 186-196Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar, 25Brown WT Wu X Fowler JF et al.Lung metastases treated by CyberKnife image-guided robotic stereotactic radiosurgery at 41 months.South Med J. 2008; 101: 376-382Crossref PubMed Scopus (45) Google Scholar, 26Yoon SM Choi EK Lee SW et al.Clinical results of stereotactic body frame based fractionated radiation therapy for primary or metastatic thoracic tumors.Acta Oncol. 2006; 45: 1108-1114Crossref PubMed Scopus (36) Google Scholar A recent retrospective study, to the best of our knowledge the first designed to compare surgery with SABR for pulmonary oligometastases, suggested comparable rates of local control and PFS.33Widder J Klinkenberg TJ Ubbels JF Wiegman EM Groen HJ Langendijk JA Pulmonary oligometastases: metastasectomy or stereotactic ablative radiotherapy?.Radiother Oncol. 2013; 107: 409-413Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar In this single institutional experience of consecutive patients, SABR was offered as a second choice to patients not eligible for surgery. Most surgical patients (n = 68) had colorectal cancer (57%) or sarcoma (27%), while most SABR patients (n = 42) had colorectal (74%) or NSCLC (14%). With a median follow-up of 43 months, overall survival at 5 years was 41% for metastasectomy and 49% for SABR,. These results are promising, but the absence of prospective trials, large retrospective studies with adequate follow-up, meta-analyses, or collaborative network observational studies hampers our ability to evaluate the role of SABR in this setting. Metastasectomy should still be regarded as the standard therapeutic option for pulmonary oligometastases, as SABR has not yet been evaluated in a large prospective study. The biological mechanisms of radiation-induced tumor cell death at fraction sizes greater than 8 to 10 Gy are likely more complex than previously thought. In addition to DNA damage, experimental models suggest that endothelial membrane alterations occur after high radiation doses, inducing sphingomyelin-mediated endothelial apoptosis, which lead to microvasculature dysfunction.34Fuks Z Kolesnick R Engaging the vascular component of the tumor response.Cancer Cell. 2005; 8: 89-91Abstract Full Text Full Text PDF PubMed Scopus (340) Google Scholar A combination of radiation-induced endothelial damage and direct tumor cell killing may explain the “tumor ablative” effect of stereotactic radiotherapy. Data from the treatment of primary lung cancer suggest that biologically effective doses higher than 100 Gy (with tumors α/β = 10 Gy) are needed to achieve a tumor control probability of more than 90%.35Onishi H Shirato H Nagata Y et al.Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: updated results of 257 patients in a Japanese multi-institutional study.J Thorac Oncol. 2007; 2: S94-S100Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar This prescription criterion can be reasonably extended to metastatic lung lesions. However, some uncertainties exist, mainly related to the variability in dose calculation algorithms and dose prescription conventions (in some studies, biologically effective dose values are calculated at the periphery, while in others, the isocenter). More recent data support the effectiveness of lower doses (prescribed to the planning target volume margin) in primary NSCLC, using a volume-adapted dose/fractionation schedules (with a minimal dose of 80 Gy in 2 Gy equivalents).36Trakul N Chang CN Harris J et al.Tumor volume-adapted dosing in stereotactic ablative radiotherapy of lung tumors.Int J Radiat Oncol Biol Phys. 2012; 84: 231-237Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Technical considerations related to simulation, planning, and delivery, continue to evolve, including technical advances in patient immobilization (frameless devices), set-up error correction (improved image guidance), respiratory motion management (respiratory gating, four-dimensional CT, tumor tracking), and treatment planning. Specific dose constraints for thoracic normal structures, adapted for different fractionation schedules, are also widely available.37Benedict SH Yenice KM Followill D et al.Stereotactic body radiation therapy: the report of AAPM Task Group 101.Med Phys. 2010; 37: 4078-4101Crossref PubMed Scopus (1303) Google Scholar Current clinical trials evaluating the role for surgery or SABR for oligometastatic cancer include patients with a heterogeneous group of primary tumors. PulMiCC38A randomised trial of pulmonary metastasectomy in colorectal cancer (PulMiCC).Available at: http://clinicaltrials.gov/ct2/show/NCT01106261Google Scholar is a randomized trial comparing surgery to active surveillance for pulmonary oligometastases in colorectal cancer. The COMET39Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic tumors (SABR-COMET).Available at: http://clinicaltrials.gov/ct2/show/NCT01446744?term=NCT01446744&rank=1Google Scholar phase II trial randomizes patients to st" @default.
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• W2080765629 title "Stereotactic Ablative Radiotherapy for Pulmonary Oligometastases and Oligometastatic Lung Cancer" @default.
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