Surgical Intervention for Pulmonary Metastases
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Introduction: Autopsy studies of persons who died of cancer have shown the lungs to be the sole site of metastasis in about 20% of cases. The resection of pulmonary metastases is indicated for palliative purposes if they contain a large volume of necrotic tumor, infiltrate the thoracic wall to produce pain, or cause hemoptysis or retention pneumonia. Metastasectomy with curative intent may be indicated for carefully selected patients.
Methods: This review is based on a selective search of the PubMed database for articles that were published from 2006 to 2011 and contained the keywords “pulmonary metastasectomy,” “lung resection of metastasis,” and “lung metastasectomy.”
Results: No prospective comparative trials have been performed to date that might provide evidence for prolongation of survival by pulmonary metastasectomy; nor have there been any randiomized, controlled trials yielding evidence that would assist in the decision whether to treat pulmonary metastases with surgery, radiotherapy, or chemotherapy (or some combination of these). The indication for surgery is a function of the histology of the primary tumor, the number and location of metastases, the lung capacity that is expected to remain after surgery, and the opportunity for an R0 resection. Favorable prognostic factors include a long disease-free interval between the treatment of the primary tumor and the discovery of pulmonary metastases, the absence of thoracic lymph node metastases, and a small number of pulmonary metastases. The reported 5-year survival rates after pulmonary metastasectomy, depending on the primary tumor, are 35.5% to 47% for renal-cell carcinoma, 39.1% to 67.8% for colorectal cancer, 29% to 52% for soft-tissue sarcoma, 38% to 49.7% for osteosarcoma, and 79% to 94% for non-seminomatous germ-cell tumors. For the latter two types of tumor, chemotherapy is the most beneficial form of treatment for long-term survival.
Conclusion: When there is no good clinical alternative, the resection of pulmonary metastases can give some patients long-lasting freedom from malignant disease. Patients should be carefully selected on the basis of clinical staging with defined prognostic indicators.
Pulmonary metastases are often found in advanced metastatization from carcinoma of the colon and rectum, kidney, breast, prostate, and oropharynx. In addition, chorionic carcinoma, osteosarcoma, soft tissue sarcoma, testicular tumors, Ewing sarcoma, and thyroid carcinoma all metastasize preferentially to the lungs.
If metastases are restricted to the lungs, the use of surgery within the overall oncological treatment is justified.
However, since a prediction of survival cannot be done without an operation, and the utility of surgery has not yet been tested in a prospective randomized study, the decision for or against metastasectomy must be made on a case-by-case basis (e1).
The aim of this review article is to give an up-to-date overview of surgical intervention for pulmonary metastases, based on a selective literature search of PubMed using the search terms “pulmonary metastasectomy”, “lung resection of metastasis,” and “lung metastasectomy.” Radiotherapy will also be discussed as an alternative local treatment method.
Principles for selection of patients for metastasectomy
As early as 1965, Thomford et al. put forward principles for patient selection that largely still apply today (1). The criteria for selecting patients to undergo surgical resection of lung metastases are:
- Technical resectability
- Tolerable general and functional surgical risk
- Control of the primary tumor process, and
- Exclusion of any further, extrathoracic metastasis.
In patients with widespread diffuse pulmonary metastases, or if the lesions are technically or functionally inoperable, local interventions such as surgery and radiotherapy are at best palliative.
In 1991 the International Registry of Lung Metastasis was constituted with the aim of developing a rationale of surgical intervention for lung metastases (2). To this end, 5206 patients who had undergone pulmonary metastasectomy with curative intent and with various primary tumor histologies were analyzed. Patients with complete resection (R0) of a solitary disease focus and a disease-free interval of more than 3 years after surgery to treat the primary tumor showed the most favorable prognosis. Although this study contained no control group of nonoperated patients, the significantly more favorable 5-year survival after R0 resection (36%) compared to incomplete resection (13%) indicates the chances of success of metastasectomy (2). Operative mortality was 1%.
Today, the decision for surgical metastasectomy with curative intent should be taken by an interdisciplinary tumor board on a case-by-case basis. If no reasonable treatment options exist, the decision for surgical resection may in some cases be made even in the presence of unfavorable prognostic factors such as synchronous metastases.
Resection of recurrent metastases
In patients who show a solitary recurrent metastasis in the lung, it should be investigated whether repeat resection is indicated. A longer time interval between the first metastasectomy and the appearance of recurring metastases appears to be prognostically more favorable (e2). Jaklitsch and co-authors (e3) have shown for various primary tumors that patients who undergo one recurrence metastasectomy achieved a median survival time of more than 60 months; with two recurrence metastasectomies median survival was 34.7 months, and with three or more it was 45.6 months. Patients in whom further surgery appeared impossible had a median survival of 8 months.
Staging examinations depend on the underlying tumor: usually, abdominal ultrasonography and computed tomography (CT) of the abdomen, bone scintigraphy, and cranial magnetic resonance imaging (MRI) are carried out.
Local tumor recurrence must always be ruled out by specialist examinations. Investigation techniques usually include CT or MRI of the primary tumor region and, for colorectal tumors, colonoscopy.
CT is essential in the planning of lung metastasectomy (e4). FDG-PET (fluorodeoxyglucose-labeled positron emission tomography) enables extrathoracic tumor manifestations to be ruled out while at the same time characterizing pulmonary focuses of disease on a metabolic basis. This last can be important especially in the case of a solitary pulmonary disease focus or thoracic lymph node involvement (e5, e6). MRI, on the other hand, has not improved the diagnosis of lung metastases compared with conventional CT. It is specifically indicated for showing tumor invasion of the great vessels, chambers of the heart, chest wall, and spinal column, and can be helpful in ruling out synchronous liver metastases.
Lesions may remain after chemotherapy in the form of “sterilized metastases.” Histologically, in the best case these formations contain fibrosis and necrosis but no viable tumor cells (Figure 1).
Flexible tracheobronchoscopy is a standard component of the preoperative diagnostic workup. Its purpose is to allow evaluation of the mucosa and secure confirmation of the histology of centrally located metastases. In addition, it can be helpful, when used in combination with endobronchial ultrasound, in determining the status of the peribronchial and mediastinal lymph nodes (e7).
To secure the histology of peripheral foci up to 3 cm in size, video-assisted thoracic surgery (VATS) has become established for use as a diagnostic procedure with a low complication rate. How far lung metastasectomy by VATS can be used as a curative procedure to achieve local radical resection comparable with that achieved by thoracotomy has yet to be studied.
In one recent prospective randomized study, malignant pulmonary foci that had not been detected by preoperative CT were detected in 20% of patients by intraoperative palpation (3). Hence, so far thoracoscopic procedures have not been generally recommended for curative intent, since the lung tissues are not accessible to palpation as they are in the open procedure (e8).
The standard procedure is a circumscribed atypical (lung tissue sparing) resection; more rarely, anatomic resection such as pulmonary segmentectomy or lobectomy is required (Figure 2).
Central metastases involving structures near the hilum may necessitate pulmonectomy. If the functional reserve does not permit anatomic resection, atypical resection in central lung segments or of multiple metastases using a neodymium:YAG laser must be attempted (4).
Postoperative complications are reported in 10% to 15% of patients after lung metastasectomy. The main ones are recurrent postoperative secretion retention leading to atelectasis and pneumonia, cardiac arrhythmias, and bronchopleural fistulas. Morbidity is determined mainly by the patient’s general condition, the surgical approach, and the extent of the resection (e9, e10).
For a number of tumor entities, involvement of intrathoracic lymph node stations as a sign of tumor dissemination is associated with a significantly poorer prognosis (5, 6). The question of the necessity and extent of thoracic lymph node dissection in addition to metastasectomy has not yet been adequately answered. According to a survey of European thoracic surgeons, in most hospitals lymph nodes are merely sampled (e11).
Stereotactic radiotherapy is an effective and at the same time noninvasive, tissue-preserving treatment alternative for solitary lung metastases in functionally inoperable patients. With detailed radiation planning and accurate irradiation, biologically effective doses totaling more than 100 Gy can be delivered in one to five dose fractions (e12). A steep dose gradient at the margin of the lesion ensures that surrounding healthy tissue is preserved as much as possible.
Even in the case of metastatic melanoma and renal cell carcinoma, which are regarded as radioresistant, stereotactic radiotherapy allows local control rates of 88% after 18 months (e13). Because of the small radiation volumes, treatment-related side effects are rare (e12).
Special aspects of particular primary tumors
Lung metastatectomy is a treatment option in 1% to 2% of patients with colorectal carcinoma (e14). The following are regarded as unfavorable prognostic factors after lung metastatectomy (Table 1):
- Histologically confirmed thoracic lymph node involvement
- Short disease-free interval
- Raised serum CEA (carcinoembryonic antigen) tumor marker
- Multiple lung metastases (7).
If synchronous liver metastases are present, a 5-year survival rate of 42% is reported after sequential lung and liver metastasectomy. Metachronous metastases are regarded as prognostically more favorable than synchronous metastases, as is the appearance of liver metastases before lung metastases (e15, e16).
The role of adjuvant and neoadjuvant chemotherapy combined with liver metastasectomy is currently under discussion (8). To what extent similar approaches can be developed for metastasectomy in the lung remains to be seen.
Renal cell carcinoma
Renal cell carcinoma (Table 1) metastasizes preferentially to the lung, either hematogenically or lymphogenically.
Although systemic therapy with tyrosine kinase inhibitors and mTOR inhibitors is associated with an improvement in progression-free survival, lung metastasectomy continues to be accepted within the framework of treatment with curative intent (9, e17).
Factors that are favorable for surgery are metachronous, solitary foci or a few peripheral lesions. A 10-year survival rate after lung metastasectomy of 42% has been reported (10). Synchronous occurrence of thoracic lymph node metastases, however, which is relatively frequent (30% to 45% of cases), is associated with a much less favorable prognosis. Mean survival of patients with mediastinal and pulmonary lymph node involvement has been reported as 26 to 29 months, compared to 64 to 92 months without lymph node metastases (5, 6). For this reason, patients with mediastinal lymph node metastases should not be assigned to surgery with curative intent.
Advanced breast cancer (Table 2) often infiltrates the lungs and pleurae by direct invasion or lymphogenic or hematogenic dissemination. Patients with isolated lung metastases are rare; usually, local or diffuse lymphangitis with single or multiple lung metastases is found.
For patients with metachronous metastases and a limited number of foci, predominantly in one pulmonary lobe, 5-year survival rates of 40% to 50% are reported after pulmonary metastasectomy has been carried out and all the options for systemic therapy have been used up (11, 12).
Debate exists as to the necessity of surgical resection of metastases. In a retrospective study in which patients who underwent pulmonary metastasectomy showed better long-term survival (36%) than those treated conservatively (11%), Staren et al. (e18) emphasized the importance of surgery. Tanaka et al. (13), on the other hand, point out that mean survival times of 2 to 3 years are reported in patients receiving systemic therapy alone.
Notwithstanding, solitary foci in the lungs—which are discovered in the course of tumor follow-up care—often pose a problem for the differential diagnosis. If there are no extrathoracic tumors, these foci should be surgically removed, the more so since in most of these cases a primary lung carcinoma turns out to be a secondary tumor, more rarely metastatic breast cancer or a benign lesion (e19).
Head and neck carcinomas
Distant metastases are most often found in the lung. Five-year survival rates of 20.9% to 59.4% after lung metastasectomy have been reported (14, e20); a longer disease-free interval appears to be particularly favorable. Because of their high coincidence with lung carcinoma, solitary pulmonary lesions in a patient who is locally tumor-free in the head and neck (ear, nose, and throat) should undergo diagnostic workup (Table 2). Often, however, even after histological analysis, the differential diagnosis between lung cancer and metastases remains unclear.
Over 70% of all patients with metastatic melanoma (Table 3) develop lung metastases, but only about 10% of them have lung metastases alone (e21). It frequently happens that a malignant melanoma is only diagnosed through histological analysis of newly discovered lung foci (e22).
Surgery is the procedure of choice for solitary foci, and the prognosis, with 5-year survival rates of 21.0% to 35.1% (e21, e23) is significantly better than with multiple metastases. Other significant factors for a favorable prognosis are a disease-free interval of more than 12 months before the occurrence of a lung metastasis, and the absence of thoracic lymph node metastases (e24). Because of the extensive metastasization in other organ systems, FDG-PET is particularly relevant in the preoperative staging (e25).
Nonseminomatous germ cell tumors
In nonseminomatous testicular cancer (Table 3), all lesions remaining after chemotherapy (cisplatin-based combinations) should be removed so far as possible.
Although a response to chemotherapy is often accompanied by a sharp fall in tumor markers (α-fetoprotein, β-HCG), normalization of the tumor marker values does not imply that residual tumors in the lungs and mediastinum need not be removed. These can still show viable tumor cells in the histological workup, in addition to necrosis and scar tissue. The following are regarded as indications for the resection of lung foci (e26):
- All residual tumors after chemotherapy and normalization of tumor marker values
- Lack of response to chemotherapy
- Partial response to chemotherapy
- Recurrence after chemotherapy.
In addition to a large number of metastases and advanced patient age, the demonstration of viable tumor cells in the residual tissue and an absence of tumor marker normalization have proved to be clinically unfavorable prognostic factors in patients with exclusively pulmonary metastases; 5-year survival rates of 79% to 94% have been reported in studies (15, 16, e27). Postoperatively, therefore, histologically complete remission in response to chemotherapy in patients with solitary and monolateral metastases and negative retroperitoneal lymph node status is regarded as the most favorable set of characteristics (15, 16).
Soft tissue sarcoma
Between 20% and 50% of all patients with soft tissue sarcoma (Table 4) develop lung metastases in the course of their disease, most of these being discovered as metachronous metastases in the course of follow-up care for the primary tumor (17).
Lung metastases from soft tissue sarcomas should be surgically removed so long as complete surgical resection appears technically possible, because they are usually only moderately chemosensitive (17, e28, e29).
In a retrospective nonrandomized study the natural course of patients with lung metastases showed a median survival of 11 months compared to 33 months for those who were treated surgically; however, it may be assumed that these results are biased by stringent selection of patients for surgical treatment (e28).
Favorable prognostic factors are a long disease-free interval before the appearance of lung metastasis and a low histological grade; 5-year survival rates after surgical metastasectomy are reported at between 29% and 52% (18, e29, e30).
Despite the progress in chemotherapy, radiotherapy, and surgical treatment of metastatic osteosarcoma (Table 4), the 5-year survival rates—among these patients who are mostly young—are between 20% and 40% (19–21).
Treatment of metastatic osteosarcoma today is tied to clinical studies (COSS/Cooperative Osteosarcoma Study, EURAMOS-1/European-American Osteosarcoma Study, and EUROB. O.S.S./EUROpean Bone Over 40 Sarcoma Study), is multidisciplinary, and takes into account the systemic and local manifestations (e31, e32). For synchronous lung metastases of the highly malignant osteosarcoma, this means aiming at complete resection of the lung metastases after chemotherapy and radical surgery of the primary tumor (e33). Postoperatively, therapy must be stratified according to tumor response.
Patients with primary metastatic osteosarcoma must be assumed to have a poorer prognosis than those with metachronous metastasization (e34).
Surgical resection is also considered to be particularly important for recurrent lung metastases, irrespective of whether chemotherapy is carried out (22).
For lung metastases of other primary tumors, the list of general indications applies: that is, local resection should be carried out if this is technically and functionally feasible, so long as the primary tumor has been removed or is under control and no more effective local or systemic treatment is available.
The diagnosis of lung metastases is often associated with a very poor prognosis with a short survival time. In these situations, palliative chemotherapy is usually initiated. First, however, an interdisciplinary tumor board should discuss the possibility of metastasectomy. If reasons are found for carrying out palliative resection, local radical resection is fundamentally the aim as well as symptom control (e35).
Functional operability must be confirmed before surgery in accordance with the European Respiratory Society/European Society of Thoracic Surgeons guidelines (e36).
Survival after lung metastasectomy depends on the nature of the primary tumor, and in the case of chemotherapy-sensitive tumors is related to surgery only to a limited extent. The objection that surgical resection of metastases is a local procedure applied to a disseminated disease, the success of which has not been validated in prospective randomized studies, is justified (e37). The first prospective randomized studies of the effect of surgical resection of lung metastases have been started with the PulMiCC-Trial (Pulmonary Metastasectomy in Colorectal Cancer) in colorectal carcinoma and the SMAT study (a prospective randomized multicenter phase 2 study of surgical resection of lung metastases of clear-cell renal cell carcinoma ± sunatinib therapy for 1 year) in renal cell carcinoma (23, 24). Data on lung metastasectomy can be found only in the current S1 guideline for osteosarcoma (e32) and the S3 guideline for colorectal cancer (e38). Even in these, the evidence base still rests on published results of retrospective case series.
Conflict of interest statement
Dr Egerer has received consultancy fees from MSD and lecture fees from MSD and Pfizer. She has also received third-party study funding from MSD.
Professor Thomas has received consultancy fees and reimbursement of registration fees for conferences/training events and travel costs from Lilly, Pfizer, Novartis, and Roche.
Professor Dienemann has received consultancy fees from Lilly and lecture fees from AstraZeneca.
Professor Pfannschmidt and Professor Bischof declare that no conflict of interest exists.
Manuscript received on 2 December 2011, revised version accepted on
28 March 2012.
Translated from the original German by Kersti Wagstaff, MA.
Prof. Dr. med. Joachim Pfannschmidt
Chirurgische Abteilung der Thoraxklinik am Universitätsklinikum Heidelberg
69126 Heidelberg, Germany
@For eReferences please refer to:
Department of Internal Medicine V: Hematology, Oncology and Rheumatology, Heidelberg University Hospital: PD Dr. med. Egerer
Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital: Prof. Dr. med. Bischof
Department of Thoracic Oncology at the Thoraxklinik, Heidelberg University Hospital: Prof. Dr. med. Thomas
|1.||Thomford NR, Woolner LB, Clagett OT: The surgical treatment of metastatic tumors in the lungs. J Thorac Cardiovasc Surg 1965; 49: 357–63. MEDLINE|
|2.||The International Registry of Lung Metastases: Long-term Results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997; 113: 37–47. CrossRef MEDLINE|
|3.||Cerfolio RJ, Bryant AS, McCarty TP, Minnich DJ: A prospective study to determine the incidence of non-imaged malignant pulmonary nodules in patients who undergo metastasectomy by thoracotomy with lung palpation. Ann Thorac Surg 2011; 91: 1696–700; discussion 1700–1. MEDLINE|
|4.||Rolle A, Pereszlenyi A, Koch R, Richard M, Baier B: Is surgery for multiple lung metastases reasonable? A total of 328 consecutive patients with multiple-laser metastasectomies with a new 1318-nm Nd:YAG laser. J Thorac Cardiovasc Surg 2006; 131: 1236–42. CrossRef MEDLINE|
|5.||Pfannschmidt J, Klode J, Muley T, Dienemann H, Hoffmann H: Nodal involvement at the time of pulmonary metastasectomy: experiences in 245 patients. Ann Thorac Surg 2006; 81: 448–54. CrossRef MEDLINE|
|6.||Meimarakis G, Angele MK, Schneider C, Weidenhagen R, Kalaitzis N, Molki A, et al.: Bedeutung der systematischen Lymphknotendissektion im Rahmen der Resektion pulmonaler Metastasen solider extrapulmonaler Tumoren. Zentralbl Chir 2010; 135: 556–63. CrossRef MEDLINE|
|7.||Pfannschmidt J, Hoffmann H, Dienemann H: Reported outcome factors for pulmonary resection in metastatic colorectal cancer. J Thorac Oncol 2010; 5 (6 Suppl 2): S172–8. CrossRef MEDLINE|
|8.||Neumann UP, Seehofer D, Neuhaus P: The surgical treatment of hepatic metastases in colorectal carcinoma. Dtsch Arztebl Int 2010; 107(19): 335–42. VOLLTEXT|
|9.||Staehler M: The role of metastasectomy in metastatic renal cell carcinoma. Nat Rev Urol 2011; 8: 180–1. CrossRef MEDLINE|
|10.||Chen F, Fujinaga T, Shoji T, Miyahara R, Bando T, Okubo K, et al.: Pulmonary resection for metastasis from renal cell carcinoma. Interact Cardiovasc Thorac Surg 2008; 7: 825–8. CrossRef MEDLINE|
|11.||Chen F, Fujinaga T, Sato K, Sonobe M, Shoji T, Sakai H, et al.: Clinical features of surgical resection for pulmonary metastasis from breast cancer. Eur J Surg Oncol 2009; 35: 393–7. CrossRef MEDLINE|
|12.|| Welter S, Jacobs J, Krbek T, Tötsch M, Stamatis G: Pulmonary metastases of breast cancer. When is resection indicated? |
Eur J Cardiothorac Surg 2008; 34: 1228–34. CrossRef MEDLINE
|13.||Tanaka F, Li M, Hanaoka N, et al.: Surgery for pulmonary nodules in breast cancer patients. Ann Thorac Surg 2005; 79: 1711–4; discussion 1714–5. MEDLINE|
|14.||Shiono S, Kawamura M, Sato T, Okumura S, Nakajima J, Yoshino I, et al.: Pulmonary metastasectomy for pulmonary metastases of head and neck squamous cell carcinomas. Ann Thorac Surg 2009; 88: 856–60. CrossRef MEDLINE|
|15.|| Kesler KA, Kruter LE, Perkins SM, Rieger KM, Sullivan KJ, |
Runyan ML, et al.: Survival after resection for metastatic testicular nonseminomatous germ cell cancer to the lung or mediastinum. Ann Thorac Surg 2011; 91: 1085–93; discussion 1093. CrossRef MEDLINE
|16.||Pfannschmidt J, Hoffmann H, Dienemann H: Thoracic metastasectomy for nonseminomatous germ cell tumors. J Thorac Oncol 2010; 5 (6 Suppl 2): S182–6. CrossRef MEDLINE|
|17.||Gadd MA, Casper ES, Woodruff JM, McCormack PM, Brennan MF: Development and treatment of pulmonary metastases in adult patients with extremity soft tissue sarcoma. Ann Surg 1993; 218: 705–12. CrossRef MEDLINE PubMed Central|
|18.||Predina JD, Puc MM, Bergey MR, Sonnad SS, Kucharczuk JC, Staddon A, et al.: Improved survival after pulmonary metastasectomy for soft tissue sarcoma. J Thorac Oncol 2011; 6: 913–9. CrossRef MEDLINE|
|19.||Briccoli A, Rocca M, Salone M, et al.: Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer 2005; 104: 1721–5. CrossRef MEDLINE|
|20.||Harting MT, Blakely ML, Jaffe N, Cox CSJ, Hayes-Jordan A, Benjamin RS, et al.: Long-term survival after aggressive resection of pulmonary metastases among children and adolescents with osteosarcoma. J Pediatr Surg 2006; 41: 194–9. CrossRef MEDLINE|
|21.||Tsuchiya H, Kanazawa Y, Abdel-Wanis ME, Asada N, Abe S, Isu K, et al.: Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: the Japanese Musculoskeletal Oncology Group study. J Clin Oncol 2002; 20: 3470–7. CrossRef MEDLINE|
|22.||Briccoli A, Rocca M, Salone M, Guzzardella GA, Balladelli A, Bacci G: High grade osteosarcoma of the extremities metastatic to the lung: long-term results in 323 patients treated combining surgery and chemotherapy, 1985–2005. Surg Oncol 2010; 19: 193–9. CrossRef MEDLINE|
|23.||Treasure T, Fallowfield L, Lees B, Farewell V: Pulmonary metastasectomy in colorectal cancer: the PulMiCC trial. Thorax 2012; 67: 185–7. CrossRef MEDLINE|
|24.||Rexer H: Dringend Patientenzuweisungen zu AUO-Studie beim metastasierten Nierenzellkarzinom gesucht. Prospektiv randomisierte multizentrische Phase-II-Studie zur Metastasenresektion von Lungenfiliae beim klarzelligen Nierenzellkarzinom ± adjuvante Sunitinib-Therapie über 1 Jahr (SMAT – AN 20/04 der AUO). Urologe 2012; 51: 252–3. CrossRef MEDLINE|
|e1.||Fey MF, Sauter C, Alberto P: Chemotherapie gastrointestinaler Karzinome und nicht-kleinzelliger Lungenkarzinome: eine Kontroverse. Schweiz Med Wochenschr 1996; 126: 872–8. MEDLINE|
|e2.||Kaifi JT, Gusani NJ, Deshaies I, et al.: Indications and approach to surgical resection of lung metastases. J Surg Oncol 2010; 102: 187–95. MEDLINE|
|e3.||Jaklitsch MT, Mery CM, Lukanich JM, Richards WG, Bueno R, Swanson SJ, et al.: Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest. J Thorac Cardiovasc Surg 2001; 121: 657–67. MEDLINE|
|e4.||Pfannschmidt J, Bischoff M, Muley T, Kunz J, Zamecnik P, Schnabel PA, et al.: Diagnosis of pulmonary metastases with helical CT: the effect of imaging techniques. Thorac Cardiovasc Surg 2008; 56: 471–5. MEDLINE|
|e5.||Aquino SL: Imaging of metastatic disease to the thorax. Radiol Clin North Am 2005; 43: 481–95. MEDLINE|
|e6.||Pastorino U, Veronesi G, Landoni C, Leon M, Picchio M, Solli PG, et al.: Fluorodeoxyglucose positron emission tomography improves preoperative staging of resectable lung metastasis. J Thorac Cardiovasc Surg 2003; 126: 1906–10. MEDLINE|
|e7.||Gompelmann D, Eberhardt R, Herth FJ: Endobronchialer Ultraschall. Radiologe 2010; 50: 692–8. MEDLINE|
|e8.||Molnar TF, Gebitekin C, Turna A: What are the considerations in the surgical approach in pulmonary metastasectomy? J Thorac Oncol 2010; 5 (6 Suppl 2): S140–4. MEDLINE|
|e9.||Roth JA, Pass HI, Wesley MN, White D, Putnam JB, Seipp C: Comparison of median sternotomy and thoracotomy for resection of pulmonary metastases in patients with adult soft-tissue sarcomas. Ann Thorac Surg 1986; 42: 134–8. MEDLINE|
|e10.||Vogt-Moykopf I, Krysa S, Bülzebruck H, Schirren J: Surgery for pulmonary metastases. The Heidelberg experience. Chest Surg Clin N Am 1994; 4: 85–112. MEDLINE|
|e11.||Internullo E, Cassivi SD, Van Raemdonck D, Friedel G, Treasure T: Pulmonary metastasectomy: a survey of current practice amongst members of the European Society of Thoracic Surgeons. J Thorac Oncol 2008; 3: 1257–66. MEDLINE|
|e12.||Stinauer MA, Kavanagh BD, Schefter TE, Gonzalez R, Flaig T, Lewis K, et al.: Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control. Radiat Oncol 2011; 6: 34. MEDLINE|
|e13.||Sampson MC, Katz A, Constine LS: Stereotactic body radiation for extracranial oligomeatastases: does the sword have a double edge? Semin Radiat Oncol 2006; 16: 67–76. CrossRef MEDLINE|
|e14.||Wade TP, Virgo KS, Li MJ, Callander PW, Longo WE, Johnson FE: Outcomes after detection of metastatic carcinoma of the colon and rectum in a national hospital system. J Am Coll Surg 1996; 182: 353–61. MEDLINE|
|e15.||Pfannschmidt J, Dienemann H, Hoffmann H: Surgical resection of pulmonary metastases from colorectal cancer: a systematic review of published series. Ann Thorac Surg 2007; 84: 324–38. CrossRef MEDLINE|
|e16.||Neeff H, Hörth W, Makowiec F, Fischer E, Imdahl A, Hopt UT, Passlick B: Outcome after resection of hepatic and pulmonary metastases of colorectal cancer. Journal of Gastrointestinal Surgery 2009; 13: 1813–20. MEDLINE|
|e17.||Karam JA, Rini BI, Varella L, Garcia JA, Dreicer R, Choueiri TK, et al.: Metastasectomy after targeted therapy in patients with advanced renal cell carcinoma. J Urol 2011; 185: 439–44. MEDLINE|
|e18.||Staren ED, Salerno C, Rongione A, Witt TR, Faber LP: Pulmonary resection for metastatic breast cancer. Arch Surg 1992; 127: 1282–4. MEDLINE|
|e19.||Rena O, Papalia E, Ruffini E, et al.: The role of surgery in the management of solitary pulmonary nodule in breast cancer patients. Eur J Surg Oncol 2007; 33: 546–50. MEDLINE|
|e20.||Chen F, Sonobe M, Sato K, Fujinaga T, Shoji T, Sakai H, et al.: Pulmonary resection for metastatic head and neck cancer. World J Surg 2008; 32: 1657–62. MEDLINE|
|e21.||Petersen RP, Hanish SI, Haney JC, Miller CC3, Burfeind WRJ, Tyler DS, et al.: Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma. J Thorac Cardiovasc Surg 2007; 133: 104–10. MEDLINE|
|e22.||Balch CM, Soong SJ, Murad TM, Smith JW, Maddox WA, Durant JR: A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III). J Clin Oncol 1983; 1: 126–34. MEDLINE|
|e23.||Schuhan C, Muley T, Dienemann H, Pfannschmidt J: Survival after pulmonary metastasectomy in patients with malignant melanoma. Thorac Cardiovasc Surg 2011; 59: 158–62. MEDLINE|
|e24.||Harpole DHJ, Johnson CM, Wolfe WG, George SL, Seigler HF: Analysis of 945 cases of pulmonary metastatic melanoma. J Thorac Cardiovasc Surg 1992; 103: 743–8; discussion 748–50. MEDLINE|
|e25.||Dalrymple-Hay MJ, Rome PD, Kennedy C, Fulham M, McCaughan BC: Pulmonary metastatic melanoma—the survival benefit associated with positron emission tomography scanning. Eur J Cardiothorac Surg 2002; 21: 611–4; discussion 614–5. CrossRef MEDLINE|
|e26.||Johnston MR, De Perrot M: Metastatic cancer to the lung. In: Devita Jr VT, Hellman S, Rosenberg SA (eds.): Cancer, Principles and Practice of Oncology. Philadelphia: Lippincott Williams & Wilkins; 2005.|
|e27.||Besse B, Grunenwald D, Flechon A, Caty A, Chevreau C, Culine S, et al.: Nonseminomatous germ cell tumors: assessing the need for postchemotherapy contralateral pulmonary resection in patients with ipsilateral complete necrosis. J Thorac Cardiovasc Surg 2009; 137: 448–52. MEDLINE|
|e28.||Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF: Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg 1999; 229: 602–10; discussion 610–2. MEDLINE PubMed Central|
|e29.||Canter RJ, Qin LX, Downey RJ, Brennan MF, Singer S, Maki RG: Perioperative chemotherapy in patients undergoing pulmonary resection for metastatic soft-tissue sarcoma of the extremity : a retrospective analysis. Cancer 2007; 110: 2050–60. MEDLINE|
|e30.||Pfannschmidt J, Klode J, Muley T, Dienemann H, Hoffmann H: Pulmonary metastasectomy in patients with soft tissue sarcomas: experiences in 50 patients. Thorac Cardiovasc Surg 2006; 54: 489–92. MEDLINE|
|e31.||Smeland S, Wiebe T, Böhling T, Brosjö O, Jonsson K, Alvegård TA: Chemotherapy in osteosarcoma. The Scandinavian Sarcoma Group experience. Acta Orthop Scand Suppl 2004; 75: 92–8. MEDLINE|
|e32.||Bielack S: Osteosarkome. Interdisziplinäre S1 Leitlinie der Deutschen Krebsgesellschaft und der Gesellschaft für Pädiatrische Onkologie und Hämatologie. Available at: www.awmf.org/uploads/tx_szleitlinien/025–005l_S1_Osteosarkome_2011–04.pdf [Last accessed on 9 March 2012].|
|e33.||Bacci G, Rocca M, Salone M, Balladelli A, Ferrari S, Palmerini E, et al.: High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions. J Surg Oncol 2008; 98: 415–20. MEDLINE|
|e34.||Huang YM, Hou CH, Hou SM, Yang RS: The metastasectomy and timing of pulmonary metastases on the outcome of osteosarcoma patients. Clin Med Oncol 2009; 3: 99–105. MEDLINE PubMed Central|
|e35.||Inderbitzi R, Rolle A: Chirurgische Palliation im Thoraxbereich bei primären und sekundären Malignomen. Ther Umsch 2001; 58: 435–41. MEDLINE|
|e36.||Brunelli A, Charloux A, Bolliger CT, Rocco G, Sculier JP, Varela G, et al.: ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy). Eur Respir J 2009; 34: 17–41. MEDLINE|
|e37.||Treasure T, Utley M, Hunt I: When professional opinion is not enough. BMJ 2007; 334: 831–2. CrossRef MEDLINE PubMed Central|
|e38.||Schmiegel W, Pox C, Reinacher-Schick A, Adler G, Arnold D, Fleig W, et al.: S3 guidelines for colorectal carcinoma: results of an evidence-based consensus conference on February 6/7, 2004 and June 8/9, 2007 (for the topics IV, VI and VII). Z Gastroenterol 2010; 48: 65–136. MEDLINE|
|e39.||Watanabe K, Nagai K, Kobayashi A, Sugito M, Saito N: Factors influencing survival after complete resection of pulmonary metastases from colorectal cancer. Br J Surg 2009; 96: 1058–65. CrossRef MEDLINE|
|e40.||Riquet M, Foucault C, Cazes A, Mitry E, Dujon A, Le Pimpec Barthes F, et al.: Pulmonary resection for metastases of colorectal adenocarcinoma. Ann Thorac Surg 2010; 89: 375–80. MEDLINE|
|e41.||Welter S, Jacobs J, Krbek T, Poettgen C, Stamatis G: Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer. Eur J Cardiothorac Surg 2007; 31: 167–72. MEDLINE|
|e42.||Meimarakis G, Angele M, Staehler M, Clevert DA, Crispin A, Rüttinger D, et al.: Evaluation of a new prognostic score (Munich score) to predict long-term survival after resection of pulmonary renal cell carcinoma metastases. Am J Surg 2011; 202: 158–67. MEDLINE|
|e43.||Kanzaki R, Higashiyama M, Fujiwara A, Tokunaga T, Maeda J, Okami J, et al.: Long-term results of surgical resection for pulmonary metastasis from renal cell carcinoma: a 25-year single-institution experience. Eur J Cardiothorac Surg 2011; 39: 167–72. MEDLINE|
|e44.||Kawashima A, Nakayama M, Oka D, Sato M, Hatano K, Mukai M, et al.: Pulmonary metastasectomy in patients with renal cell carcinoma: a single-institution experience. Int J Clin Oncol 2011; 16: 660–50. MEDLINE|
|e45.||Planchard D, Soria JC, Michiels S, Grunenwald D, Validire P, Caliandro R, et al.: Uncertain benefit from surgery in patients with lung metastases from breast carcinoma. Cancer 2004; 100: 28–35. MEDLINE|
|e46.||Shiono S, Kawamura M, Sato T, Okumura S, Nakajima J, Yoshino I, et al.: Pulmonary metastasectomy for pulmonary metastases of head and neck squamous cell carcinomas. Ann Thorac Surg 2009; 88: 856–60. MEDLINE|
|e47.||Winter H, Meimarakis G, Hoffmann G, Hummel M, Rüttinger D, Zilbauer A, et al.: Does surgical resection of pulmonary metastases of head and neck cancer improve survival? Ann Surg Oncol 2008; 15: 2915–26. MEDLINE|
|e48.||Andrews S, Robinson L, Cantor A, DeConti RC: Survival after surgical resection of isolated pulmonary metastases from malignant melanoma. Cancer Control 2006; 13: 218–23. MEDLINE|
|e49.||Pfannschmidt J, Zabeck H, Muley T, Dienemann H, Hoffmann H: Pulmonary metastasectomy following chemotherapy in patients with testicular tumors: experience in 52 patients. Thorac Cardiovasc Surg 2006; 54: 484–8. CrossRef MEDLINE|
|e50.||Letourneau PA, Xiao L, Harting MT, Lally KP, Cox CS, Andrassy RJ, Hayes-Jordan AA: Location of pulmonary metastasis in pediatric osteosarcoma is predictive of outcome. J Pediatr Surg 2011; 46: 1333–7. MEDLINE|
|e51.||Diemel KD, Klippe HJ, Branscheid D: Pulmonary metastasectomy for osteosarcoma: is it justified? Recent Results Cancer Res 2009; 179: 183–208. MEDLINE|