Extracranial oligometastases: a subset of metastases curable with stereotactic radiotherapy.

The term oligometastases, introduced in 1995 and detailed more recently, describes an intermediate state of cancer spread between localized disease and widespread metastases. Metastases from solid tumors are regarded as representative of disseminated cancer and are not considered curable, with the rare exception, such as germ cell tumors. By contrast, evidence has emerged that patients with limited metastatic disease, such as liver metastasis from colon or rectal cancer, can be cured by removal of the metastasis, drawing increased focus on the potential for intermediate states of metastatic cancer involvement. The implication of the concept of an oligometastatic state is that metastatic disease may be cured with metastasis-directed therapy. As a further conceptual refinement, Niibe et al have suggested the concept of oligorecurrence to consider patients with a limited number of metastases and controlled primary tumors as a group with an improved prognosis as compared with patients with limited metastasis and uncontrolled primary tumors. The oligometastatic hypothesis is distinct from other potentially important uses of radiotherapy and surgery in metastatic disease, such as consolidation of chemotherapy responses or as an application of the Norton-Simon hypothesis, which predicts that effectiveness of chemotherapy is proportional to the growth rate of the tumor and that the fastest growth rates occur in nonbulky tumors. Aggressive local therapy to metastatic lesions can downsize tumors, and the remaining cells might therefore be more sensitive to chemotherapy. Our review will focus on extracranial oligometastases because intracranial oligometastasis is an established clinical entity where surgery, radiotherapy, and radiosurgery have defined roles supported by phase III randomized trials and detailed outcome analyses.

[1]  J. Barney,et al.  Adenocarcinoma of the Kidney with Metastasis to the Lung: Cured by Nephrectomy and Lobectomy1 , 1939 .

[2]  I. Fidler,et al.  Metastasis: Quantitative Analysis of Distribution and Fate of Tumor Emboli Labeled With 125I-5-Iodo-2′ -deoxyuridine , 1970 .

[3]  I. Fidler,et al.  Metastasis results from preexisting variant cells within a malignant tumor. , 1977, Science.

[4]  D. Ilstrup,et al.  The Natural History of Hepatic Metastases from Colorectal Cancer: A Comparison with Resective Treatment , 1984, Annals of surgery.

[5]  C. Mountain,et al.  Surgery for pulmonary metastasis: a 20-year experience. , 1984, The Annals of thoracic surgery.

[6]  L. Norton,et al.  The Norton-Simon hypothesis revisited. , 1986, Cancer treatment reports.

[7]  S Paget,et al.  THE DISTRIBUTION OF SECONDARY GROWTHS IN CANCER OF THE BREAST. , 1889 .

[8]  Y Maruyama,et al.  A randomized trial of surgery in the treatment of single metastases to the brain. , 1990, The New England journal of medicine.

[9]  M. Burt,et al.  Resection of brain metastases from non-small-cell lung carcinoma. Results of therapy. Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff. , 1992, The Journal of thoracic and cardiovascular surgery.

[10]  P. McCormack,et al.  Development and Treatment of Pulmonary Metastases in Adult Patients with Extremity Soft Tissue Sarcoma , 1993, Annals of surgery.

[11]  F. Sim,et al.  Survival after pulmonary metastasectomy in soft tissue sarcoma. Prognostic factors in 214 patients. , 1995, Acta orthopaedica Scandinavica.

[12]  I. Lax,et al.  Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. , 1995, Acta oncologica.

[13]  B. Nordlinger,et al.  Surgical resection of colorectal carcinoma metastases to the liver: A prognostic scoring system to improve case selection, based on 1568 patients , 1996, Cancer.

[14]  M Buyse,et al.  Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. , 1997, The Journal of thoracic and cardiovascular surgery.

[15]  M. Burt,et al.  The role of surgery in the treatment of clinically isolated adrenal metastasis , 1998, Cancer.

[16]  J P Pignon,et al.  Resection of liver metastases from colorectal cancer: the real impact of the surgical margin. , 1998, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[17]  B. Plaud,et al.  Resection of liver metastases from a noncolorectal primary: indications and results based on 147 monocentric patients. , 1998, Journal of the American College of Surgeons.

[18]  L. Einhorn,et al.  Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  L H Blumgart,et al.  Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. , 1999, Annals of surgery.

[20]  M. Riquet,et al.  Surgical management of non-small cell lung cancer with synchronous brain metastases. , 2001, Chest.

[21]  A. Hogg,et al.  High rate of detection of unsuspected distant metastases by pet in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy. , 2001, International journal of radiation oncology, biology, physics.

[22]  S. Ye,et al.  Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. , 2001, World journal of gastroenterology.

[23]  A. Bernard,et al.  Resection of adrenal metastases from non-small cell lung cancer: a multicenter study. , 2001, The Annals of thoracic surgery.

[24]  N. Shindo-Okada,et al.  Establishment of Cell Lines with High‐ and Low‐metastatic Potential from PC‐14 Human Lung Adenocarcinoma , 2001, Japanese journal of cancer research : Gann.

[25]  I. Fidler,et al.  The organ microenvironment and cancer metastasis. , 2002, Differentiation; research in biological diversity.

[26]  N. Restifo,et al.  Natural selection of tumor variants in the generation of “tumor escape” phenotypes , 2002, Nature Immunology.

[27]  Takanobu Kobayashi,et al.  Pulmonary metastasectomy for 165 patients with colorectal carcinoma: A prognostic assessment. , 2002, The Journal of thoracic and cardiovascular surgery.

[28]  H. Dienemann,et al.  Prognostic factors for survival after pulmonary resection of metastatic renal cell carcinoma. , 2002, The Annals of thoracic surgery.

[29]  M. Kris,et al.  A phase II trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis. , 2002, Lung cancer.

[30]  Zvi Fuks,et al.  Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis , 2003, Science.

[31]  H. Dienemann,et al.  Prognostic factors and survival after complete resection of pulmonary metastases from colorectal carcinoma: experiences in 167 patients. , 2003, The Journal of thoracic and cardiovascular surgery.

[32]  Michael Flentje,et al.  Stereotactic radiotherapy for primary lung cancer and pulmonary metastases: a noninvasive treatment approach in medically inoperable patients. , 2004, International journal of radiation oncology, biology, physics.

[33]  Maria Werner-Wasik,et al.  Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial , 2004, The Lancet.

[34]  Deepinder P. Singh,et al.  Is there a favorable subset of patients with prostate cancer who develop oligometastases? , 2004, International journal of radiation oncology, biology, physics.

[35]  R. Weichselbaum,et al.  Analysis of further disease progression in metastatic non-small cell lung cancer: implications for locoregional treatment. , 2004, International journal of oncology.

[36]  Ugo Pastorino,et al.  GENERAL THORACIC SURGERY LONG-TERM RESULTS OF LUNG METASTASECTOMY : PROGNOSTIC ANALYSES BASED ON 5206 CASES The International Registry of Lung Metastases , 2004 .

[37]  Richard Stang,et al.  Resection of colorectal liver metastases , 1997, Journal of Gastrointestinal Surgery.

[38]  Tomoyuki Kato,et al.  Preoperative probability model for predicting overall survival after resection of pulmonary metastases from colorectal cancer , 2004, The British journal of surgery.

[39]  N. Kawashima,et al.  Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. , 2004, International journal of radiation oncology, biology, physics.

[40]  Robert C. Rose,et al.  Local Radiation Therapy of B16 Melanoma Tumors Increases the Generation of Tumor Antigen-Specific Effector Cells That Traffic to the Tumor1 , 2005, The Journal of Immunology.

[41]  E. Fredlund,et al.  Hypoxia-induced dedifferentiation of tumor cells--a mechanism behind heterogeneity and aggressiveness of solid tumors. , 2005, Seminars in cell & developmental biology.

[42]  Evelyne M. Loyer,et al.  Effect of Surgical Margin Status on Survival and Site of Recurrence After Hepatic Resection for Colorectal Metastases , 2005, Annals of surgery.

[43]  D. Dodwell,et al.  The oligometastatic state in breast cancer: hypothesis or reality. , 2005, Breast.

[44]  P. Dartevelle,et al.  Surgical treatment of solitary adrenal metastasis from non-small cell lung cancer. , 2005, The Journal of thoracic and cardiovascular surgery.

[45]  Abraham Philip,et al.  Stereotactic Body Radiation Therapy (SBRT) for lung metastases , 2006, Acta oncologica.

[46]  J. Petersen,et al.  Phase II study on stereotactic body radiotherapy of colorectal metastases , 2006, Acta oncologica.

[47]  J. Massagué,et al.  Cancer Metastasis: Building a Framework , 2006, Cell.

[48]  D. Harpole,et al.  Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma. , 2007, The Journal of thoracic and cardiovascular surgery.

[49]  Yuman Fong,et al.  Actual 10-year survival after resection of colorectal liver metastases defines cure. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[50]  M. Schell,et al.  Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases. , 2007, International journal of radiation oncology, biology, physics.

[51]  Laurence Zitvogel,et al.  Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapy , 2007, Nature Medicine.

[52]  Y. Niibe,et al.  Abscopal effect of radiation on toruliform para-aortic lymph node metastases of advanced uterine cervical carcinoma--a case report. , 2007, Anticancer research.

[53]  S. Culine,et al.  Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP). , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[54]  Lei Xing,et al.  Stereotactic body radiation therapy in multiple organ sites. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  K. Herfarth,et al.  Stereotactic Single-Dose Radiotherapy of Lung Metastases , 2007, Strahlentherapie und Onkologie.

[56]  J. Massagué,et al.  Genetic determinants of cancer metastasis , 2007, Nature Reviews Genetics.

[57]  M. Schell,et al.  A prospective pilot study of curative‐intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions , 2008, Cancer.

[58]  Richard P. Hill,et al.  Hypoxia and metabolism: Hypoxia, DNA repair and genetic instability , 2008, Nature Reviews Cancer.

[59]  G. Bepler,et al.  Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[60]  A. Muhs,et al.  Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy , 2009, Breast Cancer Research and Treatment.

[61]  P. Tekkis,et al.  Evaluation of Long-term Survival After Hepatic Resection for Metastatic Colorectal Cancer: A Multifactorial Model of 929 Patients , 2008, Annals of surgery.

[62]  R. Adam,et al.  R1 Resection by Necessity for Colorectal Liver Metastases: Is It Still a Contraindication to Surgery? , 2008, Annals of surgery.

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

[64]  J. Massagué,et al.  Molecular basis of metastasis. , 2008, The New England journal of medicine.

[65]  M. Choti,et al.  Rates and Patterns of Recurrence Following Curative Intent Surgery for Colorectal Liver Metastasis: An International Multi-Institutional Analysis of 1669 Patients , 2009, Annals of surgery.

[66]  G. Lockwood,et al.  Phase I study of individualized stereotactic body radiotherapy of liver metastases. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[67]  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.

[68]  A. Muhs,et al.  Stereotactic body radiotherapy for treatment of adrenal metastases. , 2009, International journal of radiation oncology, biology, physics.

[69]  N. Kawashima,et al.  Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti–CTLA-4 Antibody , 2009, Clinical Cancer Research.

[70]  Patrick O. Brown,et al.  The Preclinical Natural History of Serous Ovarian Cancer: Defining the Target for Early Detection , 2009, PLoS medicine.

[71]  M. Wirth,et al.  Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease‐free interval and the number of metastases per patient , 2009, International journal of cancer.

[72]  R. Stock,et al.  Phase 1 study of concurrent sunitinib and image‐guided radiotherapy followed by maintenance sunitinib for patients with oligometastases , 2009, Cancer.

[73]  Colin G Orton,et al.  The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. , 2009, Medical physics.

[74]  R. Weichselbaum,et al.  Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. , 2009, Blood.

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

[76]  M. D'Angelica,et al.  Liver Resection for Metastatic Colorectal Cancer in the Presence of Extrahepatic Disease , 2009, Annals of Surgical Oncology.

[77]  H. Shirato,et al.  Oligometastases of Brain Only in Patients with Non-small Cell Lung Cancer (NSCLC) Treated with Stereotactic Irradiation (STI): A Multi-institutional Study in Japan , 2010 .

[78]  C. Cordon-Cardo,et al.  Impact of stromal sensitivity on radiation response of tumors implanted in SCID hosts revisited. , 2010, Cancer research.

[79]  H. Kennecke,et al.  Patterns of Referral and Resection Among Patients with Liver-Only Metastatic Colorectal Cancer (MCRC) , 2010, Annals of Surgical Oncology.

[80]  M. Nowak,et al.  Distant Metastasis Occurs Late during the Genetic Evolution of Pancreatic Cancer , 2010, Nature.

[81]  Y. Niibe,et al.  Oligometastases and Oligo-recurrence: The New Era of Cancer Therapy , 2010, Japanese journal of clinical oncology.

[82]  Dong Han Lee,et al.  Oligometastases confined one organ from colorectal cancer treated by SBRT , 2010, Clinical & Experimental Metastasis.

[83]  Jian Z. Wang,et al.  Stereotactic body radiation therapy for spinal metastases. , 2010, Discovery medicine.

[84]  James Ze Wang,et al.  Stereotactic radiosurgery alone for patients with 1–4 radioresistant brain metastases , 2011, Medical oncology.

[85]  R. Weichselbaum,et al.  Oligometastases revisited , 2011, Nature Reviews Clinical Oncology.

[86]  F. Petrella,et al.  A 10-Year Single-Center Experience on 708 Lung Metastasectomies: The Evidence of the “International Registry of Lung Metastases” , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[87]  R. Weichselbaum,et al.  MicroRNA Expression Characterizes Oligometastasis(es) , 2011, PloS one.

[88]  Hideomi Yamashita,et al.  Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report , 2011, Journal of medical case reports.

[89]  R. Weichselbaum,et al.  Patterns of Distant Failure and Progression in Breast Cancer: Implications for the Treatment of Oligometastatic Disease , 2011 .

[90]  Joe Y. Chang,et al.  Oligometastatic Disease at Presentation or Recurrence for Nonsmall Cell Lung Cancer , 2012, Pulmonary medicine.

[91]  W. Urba,et al.  Phase 1 Study of Stereotactic Body Radiotherapy and Interleukin-2—Tumor and Immunological Responses , 2012, Science Translational Medicine.

[92]  Oleksiy Karpenko,et al.  Oligo- and Polymetastatic Progression in Lung Metastasis(es) Patients Is Associated with Specific MicroRNAs , 2012, PloS one.

[93]  Jedd D. Wolchok,et al.  Immunologic correlates of the abscopal effect in a patient with melanoma. , 2012, The New England journal of medicine.

[94]  P. Okunieff,et al.  Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study. , 2012, International journal of radiation oncology, biology, physics.

[95]  P. Lambin,et al.  Radical Treatment of Non–Small-Cell Lung Cancer Patients with Synchronous Oligometastases: Long-Term Results of a Prospective Phase II Trial (Nct01282450) , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[96]  S. Rudra,et al.  Patterns of Failure in Esophageal Cancer -- What is the Likelihood of Limited Metastatic Failure? , 2012 .

[97]  Dong Han Lee,et al.  High dose stereotactic body radiotherapy using three fractions for colorectal oligometastases , 2012, Journal of surgical oncology.

[98]  Xianghua Luo,et al.  Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[99]  R. Weichselbaum,et al.  Stereotactic body radiotherapy for multisite extracranial oligometastases , 2012, Cancer.