Original Thoracic
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis: Analysis of 37 Cases Danjouma Housmanou Cheufou1 Stefan Welter1 Dirk Theegarten3 Georgios Stamatis1 1 Department of Thoracic Surgery and Endoscopy, Ruhrlandklinik,
University of Duisburg-Essen, Essen, Germany 2 Department of Medical Oncology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany 3 Institut of Pathology and Neuropathology, University of DuisburgEssen, Essen, Germany
Eleftherios Chalvatzoulis1
Daniel Christof2
Address for correspondence Danjouma Housmanou Cheufou, MD, Thoracic Surgeon, Department of Thoracic Surgery, Ruhrlandklinik Essen, Tüschener Weg 40, Essen 45219, Germany (e-mail: [email protected]).
Thorac Cardiovasc Surg 2014;62:612–615.
Abstract
Keywords
► surgery ► cerebral metastasis ► non-small cell lung cancer
Background At the time of diagnosis, lung cancer has often metastasized already. Brain metastases, however, are associated with a poor prognosis (median survival of less than 1 year). We evaluated the changes of the median survival after resection of the cerebral metastases and primary non-small cell lung cancer (NSCLC). Materials and Methods Between January 1999 and December 2009, 37 patients (22 men, 15 women; median age: 55.64 years; age range: 38–72 years) underwent surgery for primary NSCLC after craniotomy and removal of the synchronous single brain metastasis. The overall survival was evaluated and risk factors identified. Results Mediastinal lymph node involvement was excluded with mediastinoscopy in 26 of the 37 patients. Postoperative N-stage was N0, N1, and N2 in 16 (43%), 10 (27%), and 11 (30%) patients, respectively. Histology was squamous cell carcinoma in 10 (27%), adenocarcinoma in 20 (54%), and large cell carcinoma in 7 (19%). The employed type of resection was anatomical segmentectomy in 6 and lobectomy in 31 patients. The 30-day mortality was 0% and postoperative complications occurred in 12 patients only (32%). The overall 1 and 2 years survival were 62 and 24%, respectively. None of the factors age, sex, tumor histology, primary location of the tumor, type of resection, adjuvant chemotherapy, or nodal status affected survival in the univariate analysis. Conclusions The oncologic lung resection of NSCLC after the resection of a single brain metastasis can be implemented without an increased risk of complications or mortality. Despite the stage IV disease, the median survival appears encouraging.
Introduction Bronchial carcinomas remain the leading cause of cancerrelated death in industrialized countries. This cancer has often already metastasized at the time of diagnosis. Bronchial carcinomas metastasize most frequently in the central ner-
received December 2, 2013 accepted after revision April 1, 2014 published online June 25, 2014
vous system (CNS).1 Up to 30% of patients develop brain metastases during the course of their disease,2,3 with a prevalence at autopsy of up to 53%. Brain metastases have been found to be superficial, allowing the successful removal along with the primary tumor and resulting in prolongation of life.4,5 In contrast to that, the prognosis of a patient with
© 2014 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1377060. ISSN 0171-6425.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
612
brain metastases is poor without treatment, median survival ranging from 1 to 6 months only.4 In many cases, the clinical signs of metastases are the reason for the patient presentation. Approximately 34% of these patients are admitted to the hospital with neurological symptoms.5 However, metastases can occur in other organs too, including bones, adrenal glands, and liver.6 Consequently, a thorough examination is necessary before the surgical intervention. The highest occurrence of metastases, as found by autopsy, is small cell lung cancer, anaplastic large-cell carcinoma, and adenocarcinoma.4 Few studies have been published on the synchronous combined resection of brain metastases and primary nonsmall cell lung cancer (NSCLC) in the same medical center.3,6 Central aim of this study was to analyze the accumulated experience with patients after the resection of cerebral metastasis and primary NSCLC, especially focused on risk factors and overall survival.
Cheufou et al.
Fig. 1 Overall survival curve using the Kaplan–Meier method. NSCLC and brain metastasis after resection of both tumor site. NSCLC, nonsmall cell lung cancer.
Materials and Methods As a sample, 37 patients who underwent surgical treatment of synchronous single brain metastases and primary NSCLC between January 1999 and December 2009 were extracted from the institutional database. The preoperative investigation included computed tomography (CT) of the chest, abdominal CT, and brain magnetic resonance imaging or CT. After the operative removal of the single brain metastases, all patients were classified as stage IV stated by the Union for International Cancer Control (UICC) standards and discussed in the interdisciplinary tumor board. The medical records were examined for age, sex, histology and grade, postoperative tumor lymphnode metastasis (TNM) stage, mode of resection, postoperative complications, adjuvant therapy, and finally survival. In all of the cases, pulmonary resection was regarded curative. In addition, the 30-day mortality was considered and survival was estimated using the Kaplan–Meier method. Finally, the influence of variables on survival was analyzed by the log rank test for multivariate analyses (►Fig. 1).
Ethical Considerations This study was approved by the Institutional Review Board. Follow-up information was obtained by the common treatment correspondence with the primary physician or, alternatively, from the registration office.
Results The study cohort comprised 22 men and 15 women (►Fig. 2). The median age was 55.6 years, ranging from 38 to 72 years. Craniotomy and removal of the cerebral metastasis was performed in all cases at an average of 4 weeks before thoracic surgery. The main symptom was headache (37.83%), many patients complained about epilepsy; other symptoms were visual problems (5.40%), speech disorder (5.40%), and hemiparesis (13.51%). The cerebral metastases were located parietal in 13 cases (35.13%; 6 left and 7 right), occipital in 12 (32.42%; 4 left and 8 right), frontal in 8 cases (21.62%; 3 left, 5
Fig. 2 Overall survival curve men/women. NSCLC and brain metastasis after resection of both tumor site. NSCLC, non-small cell lung cancer.
right), and in the cerebellum in 4 cases (10.81%). Neoadjuvant treatment before the lung resection involved three patients who received radio/chemotherapy, one patient who received chemotherapy, and one patient who received brain radiotherapy. All other patients received chemotherapy and whole brain irradiation after lung surgery. The mediastinal involvement was clinically ruled out with mediastinoscopy in 26 patients (70%), whereas 11 patients had unsuspicious nodes only. Postoperative mediastinal stage was N0, N1, and N2 in 16 (43%), 10 (27%), and 11 (28%) patients, respectively. Then, the pathological examination revealed squamous cell carcinoma in 10 (27%), adenocarcinoma in 20 (54%), and large cell carcinomas in 7 (19%) patients. A total of 68% of the women displayed histological adenocarcinomas. Although 31 patients underwent lobectomy, the remaining 6 were subject to anatomical segmentectomy (►Fig. 3). No deaths needed to be reported in the 30 days following the pulmonary resection. Although 25 patients of the sample were free from complications, 12 patients (32%) experienced complications after lung surgery. Of these, two (5.4%) developed pneumonia, one (3%) Thoracic and Cardiovascular Surgeon
Vol. 62
No. 7/2014
613
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis
Cheufou et al.
Fig. 3 Overall survival curve. Lobectomy versus segmentectomy.
Fig. 4 Overall survival curve: Age; under 55 years versus over 55 years.
had atelectasis requiring bronchoscopy, and seven (19%) had prolonged air leak. In addition, arrhythmia was noted in one (3%) patient. Beyond all of this, there was one case of pulmonary embolism (3%), one case of empyema (3%), and one case of bleeding with the need for surgical revision (3%). The follow-up was completed for all 37 patients with a median follow-up of 17.3 months (range: 2–69). Currently, three patients are alive without any evidence of a recurrent disease. The overall survival was 62 and 24% after 1 and 2 years. Univariate analysis revealed that neither age, sex, tumor histology, primary location, type of resection, adjuvant therapy, nor nodal status significantly affected survival (►Fig. 4).
fore lung surgery. No instance of cerebral recurrence was found in this series. One report on recurrent cancer in the brain after craniotomy and whole brain radiotherapy indicates that additive procedures for cerebral local control have become an important part of the therapy.1 Even though a conventional particle accelerator can be used to deliver a boost after whole brain radiotherapy in selected patients, the benefit is not significant enough and the results are not satisfying.12 Moreover, the risk of dementia increases with high radiation doses. All patients of the sample used in this study underwent surgery without positron emission tomography (PET)/CT. A mediastinoscopy was performed on 26 (70%) of the patients. It appears that the number of mediastinoscopies can be reduced by using PET scans or endobronchial ultrasound as substitutes. At the time of this study, neither of these diagnostic tools had been available at the institution. In contrast to that, these tools are now part of the standard clinical evaluation of all patients with bronchial carcinoma. In this series, a large number of patients had tumors categorized as N1 (27%) and N2 (28%). However, there was no statistical difference in survival compared with the other patients. This observation was also made by Burt and associates, who found no difference in survival between patients with stages I and II NSCLC compared with patients with stages III and IV disease.12 They also found that one patient with a stage N1 disease was still alive 5 years after lung resection, and another patient with a stage N2 disease was still alive 32 months after lung resection. Of the 11 patients in stage N2, we found that 8 of them had paraesophageal lymph node metastases which could not be detected with standard mediastinoscopy. Only three patients were subcarinal in stage N2. Of these, two did not undergo mediastinoscopy due to unsuspicious lymph nodes in the CT scan. Rossi et al compared the outcome of patients after the resection of both tumor sites and whole brain radiotherapy to that of patients receiving resection of only the cranial tumor without resection of NSCLC.13 They found that the 1-year survival of patients without resection of NSCLC was 15%; all
Discussion Approximately 15 to 20% of all patients with NSCLC develop brain metastases during the course of their disease.2,3 Without any treatment, the median survival time from the first diagnosis of brain metastases is approximately 1 to 6 months.4,7 The best approach to manage a single cerebral metastasis differs depending on the location, primary histology, and general condition of the patient. Corticosteroid administration in patients with brain metastases offers a rapid improvement of the neurological symptoms but does not prolong survival beyond 3 months.8 Some authors treat cerebral recurrence successfully with pemetrexed. Here, the blood– brain barrier, which normally protects CNS from cytotoxic agents, becomes less functional in the presence of brain metastases.1 We did not receive patients with small cell lung cancer. It appears that after cerebral metastasectomy with the detection of small cell lung cancer, the patients were embedded in nonsurgical concepts and not considered for surgery. The results of randomized trials revealed that the survival after craniotomy plus a whole brain radiation therapy for a single cerebral metastasis was significantly better than the survival after brain radiotherapy alone.9–11 In the presented study, all patients underwent cerebral metastasectomy beThoracic and Cardiovascular Surgeon
Vol. 62
No. 7/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
614
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis References
1 Ochi N, Yamane H, Yamagishi T, Takigawa N. Continuous peme-
2
3
4
5
6
7
8 9
10
11
12
Conclusion Combined surgical resection of both tumor sites in patients with NSCLC and single brain metastases can be implemented with low risks of mortality or morbidity and with the chance of prolonged survival. The described findings indicate that whenever possible, a surgical approach should be considered for well-evaluated patients.
13
14
15 16
Conflict of Interest There are no conflicts of interest to report.
615
trexed treatment for brain metastasis in non-small cell lung cancer —a report of two cases. Lung Cancer 2013;80(1):111–113 Kawabe T, Phi JH, Yamamoto M, Kim DG, Barfod BE, Urakawa Y. Treatment of brain metastasis from lung cancer. Prog Neurol Surg 2012;25:148–155 Billing PS, Miller DL, Allen MS, Deschamps C, Trastek VF, Pairolero PC. Surgical treatment of primary lung cancer with synchronous brain metastases. J Thorac Cardiovasc Surg 2001;122(3):548–553 Knights EM Jr. Metastatic tumors of the brain and their relation to primary and secondary pulmonary cancer. Cancer 1954;7(2): 259–265 Figlin RA, Piantadosi S, Feld R. Intracranial recurrence of carcinoma after complete surgical resection of stage I, II, and III non-small-cell lung cancer. N Engl J Med 1988;318(20):1300–1305 Magilligan DJ Jr, Duvernoy C, Malik G, Lewis JW Jr, Knighton R, Ausman JI. Surgical approach to lung cancer with solitary cerebral metastasis: twenty-five years’ experience. Ann Thorac Surg 1986; 42(4):360–364 Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322(8):494–500 Ruderman NB, Hall TC. Use of glucocorticoids in the palliative treatment of metastatic brain tumors. Cancer 1965;18:298–306 Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998;280(17):1485–1489 Vecht CJ, Haaxma-Reiche H, Noordijk EM, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 1993;33(6):583–590 Lévy A, Chargari C, Lamproglou I, Mazeron JJ, Krzisch C, Assouline A. Whole brain radiation with supplementary boost for patients for unique brain metastasis from a primitive lung cancer [in French]. Cancer Radiother 2011;15(5):426–429 Burt M, Wronski M, Arbit E, Galicich JH; Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff. Resection of brain metastases from non-small-cell lung carcinoma. Results of therapy. J Thorac Cardiovasc Surg 1992;103(3):399–410, discussion 410–411 Rossi NP, Zavala DC, VanGilder JC. A combined surgical approach to non-oat-cell pulmonary carcinoma with single cerebral metastasis. Respiration 1987;51(3):170–178 Read RC, Boop WC, Yoder G, Schaefer R. Management of nonsmall cell lung carcinoma with solitary brain metastasis. J Thorac Cardiovasc Surg 1989;98(5 Pt 2):884–890, discussion 890–891 Richards P, McKISSOCK W. Intracranial metastases. BMJ 1963; 1(5322):15–18 Griffioen GH, Toguri D, Dahele M, et al. Radical treatment of synchronous oligometastatic non-small cell lung carcinoma (NSCLC): patient outcomes and prognostic factors. Lung Cancer 2013;82(1):95–102
Thoracic and Cardiovascular Surgeon
Vol. 62
No. 7/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
died within 2 years. Patients with the resection of both sites plus the whole brain radiotherapy displayed a 1-year survival rate of 35%, and the subsequent 2-year survival rate was 25%.14 In this series, the overall survival at 1 and 2 years was at least similar or even better. The hospital mortality rate was 2% in another series and all patients surviving for more than 2 years were patients who underwent resection of both tumor sites.15 In this series, the 30-day mortality was 0%, similar to that found by Read.14 This observation confirms that the approach of surgically treating both sites can be used safely in well-selected patients. The identification of prognostic factors was not within the scope of this study. All in all, there is evidence that recommends the complete resection of both tumor sites for patients with single brain metastases and resectable tumor in the lung. The presented study revealed that neither survival nor the disease-free interval was connected to age, primary tumor or lymph node status, tumor histology, size, side, or the type of pulmonary resection. Limitations of this study can be seen in the retrospective study design and the restriction on a single-center source of experience. Furthermore, the application of pre- or postoperative chemotherapy could not be analyzed with respect to remission, nor could we analyze the pattern of recurrence in those patients who died. Some patients are reported to have died within a relatively short time span after the monitored period of 2 years. It appears likely that micrometastases which were undetectable at the time of diagnosis could have been an important factor in the death of these patients.16
Cheufou et al.
Copyright of Thoracic & Cardiovascular Surgeon is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis: Analysis of 37 Cases Danjouma Housmanou Cheufou1 Stefan Welter1 Dirk Theegarten3 Georgios Stamatis1 1 Department of Thoracic Surgery and Endoscopy, Ruhrlandklinik,
University of Duisburg-Essen, Essen, Germany 2 Department of Medical Oncology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany 3 Institut of Pathology and Neuropathology, University of DuisburgEssen, Essen, Germany
Eleftherios Chalvatzoulis1
Daniel Christof2
Address for correspondence Danjouma Housmanou Cheufou, MD, Thoracic Surgeon, Department of Thoracic Surgery, Ruhrlandklinik Essen, Tüschener Weg 40, Essen 45219, Germany (e-mail: [email protected]).
Thorac Cardiovasc Surg 2014;62:612–615.
Abstract
Keywords
► surgery ► cerebral metastasis ► non-small cell lung cancer
Background At the time of diagnosis, lung cancer has often metastasized already. Brain metastases, however, are associated with a poor prognosis (median survival of less than 1 year). We evaluated the changes of the median survival after resection of the cerebral metastases and primary non-small cell lung cancer (NSCLC). Materials and Methods Between January 1999 and December 2009, 37 patients (22 men, 15 women; median age: 55.64 years; age range: 38–72 years) underwent surgery for primary NSCLC after craniotomy and removal of the synchronous single brain metastasis. The overall survival was evaluated and risk factors identified. Results Mediastinal lymph node involvement was excluded with mediastinoscopy in 26 of the 37 patients. Postoperative N-stage was N0, N1, and N2 in 16 (43%), 10 (27%), and 11 (30%) patients, respectively. Histology was squamous cell carcinoma in 10 (27%), adenocarcinoma in 20 (54%), and large cell carcinoma in 7 (19%). The employed type of resection was anatomical segmentectomy in 6 and lobectomy in 31 patients. The 30-day mortality was 0% and postoperative complications occurred in 12 patients only (32%). The overall 1 and 2 years survival were 62 and 24%, respectively. None of the factors age, sex, tumor histology, primary location of the tumor, type of resection, adjuvant chemotherapy, or nodal status affected survival in the univariate analysis. Conclusions The oncologic lung resection of NSCLC after the resection of a single brain metastasis can be implemented without an increased risk of complications or mortality. Despite the stage IV disease, the median survival appears encouraging.
Introduction Bronchial carcinomas remain the leading cause of cancerrelated death in industrialized countries. This cancer has often already metastasized at the time of diagnosis. Bronchial carcinomas metastasize most frequently in the central ner-
received December 2, 2013 accepted after revision April 1, 2014 published online June 25, 2014
vous system (CNS).1 Up to 30% of patients develop brain metastases during the course of their disease,2,3 with a prevalence at autopsy of up to 53%. Brain metastases have been found to be superficial, allowing the successful removal along with the primary tumor and resulting in prolongation of life.4,5 In contrast to that, the prognosis of a patient with
© 2014 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1377060. ISSN 0171-6425.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
612
brain metastases is poor without treatment, median survival ranging from 1 to 6 months only.4 In many cases, the clinical signs of metastases are the reason for the patient presentation. Approximately 34% of these patients are admitted to the hospital with neurological symptoms.5 However, metastases can occur in other organs too, including bones, adrenal glands, and liver.6 Consequently, a thorough examination is necessary before the surgical intervention. The highest occurrence of metastases, as found by autopsy, is small cell lung cancer, anaplastic large-cell carcinoma, and adenocarcinoma.4 Few studies have been published on the synchronous combined resection of brain metastases and primary nonsmall cell lung cancer (NSCLC) in the same medical center.3,6 Central aim of this study was to analyze the accumulated experience with patients after the resection of cerebral metastasis and primary NSCLC, especially focused on risk factors and overall survival.
Cheufou et al.
Fig. 1 Overall survival curve using the Kaplan–Meier method. NSCLC and brain metastasis after resection of both tumor site. NSCLC, nonsmall cell lung cancer.
Materials and Methods As a sample, 37 patients who underwent surgical treatment of synchronous single brain metastases and primary NSCLC between January 1999 and December 2009 were extracted from the institutional database. The preoperative investigation included computed tomography (CT) of the chest, abdominal CT, and brain magnetic resonance imaging or CT. After the operative removal of the single brain metastases, all patients were classified as stage IV stated by the Union for International Cancer Control (UICC) standards and discussed in the interdisciplinary tumor board. The medical records were examined for age, sex, histology and grade, postoperative tumor lymphnode metastasis (TNM) stage, mode of resection, postoperative complications, adjuvant therapy, and finally survival. In all of the cases, pulmonary resection was regarded curative. In addition, the 30-day mortality was considered and survival was estimated using the Kaplan–Meier method. Finally, the influence of variables on survival was analyzed by the log rank test for multivariate analyses (►Fig. 1).
Ethical Considerations This study was approved by the Institutional Review Board. Follow-up information was obtained by the common treatment correspondence with the primary physician or, alternatively, from the registration office.
Results The study cohort comprised 22 men and 15 women (►Fig. 2). The median age was 55.6 years, ranging from 38 to 72 years. Craniotomy and removal of the cerebral metastasis was performed in all cases at an average of 4 weeks before thoracic surgery. The main symptom was headache (37.83%), many patients complained about epilepsy; other symptoms were visual problems (5.40%), speech disorder (5.40%), and hemiparesis (13.51%). The cerebral metastases were located parietal in 13 cases (35.13%; 6 left and 7 right), occipital in 12 (32.42%; 4 left and 8 right), frontal in 8 cases (21.62%; 3 left, 5
Fig. 2 Overall survival curve men/women. NSCLC and brain metastasis after resection of both tumor site. NSCLC, non-small cell lung cancer.
right), and in the cerebellum in 4 cases (10.81%). Neoadjuvant treatment before the lung resection involved three patients who received radio/chemotherapy, one patient who received chemotherapy, and one patient who received brain radiotherapy. All other patients received chemotherapy and whole brain irradiation after lung surgery. The mediastinal involvement was clinically ruled out with mediastinoscopy in 26 patients (70%), whereas 11 patients had unsuspicious nodes only. Postoperative mediastinal stage was N0, N1, and N2 in 16 (43%), 10 (27%), and 11 (28%) patients, respectively. Then, the pathological examination revealed squamous cell carcinoma in 10 (27%), adenocarcinoma in 20 (54%), and large cell carcinomas in 7 (19%) patients. A total of 68% of the women displayed histological adenocarcinomas. Although 31 patients underwent lobectomy, the remaining 6 were subject to anatomical segmentectomy (►Fig. 3). No deaths needed to be reported in the 30 days following the pulmonary resection. Although 25 patients of the sample were free from complications, 12 patients (32%) experienced complications after lung surgery. Of these, two (5.4%) developed pneumonia, one (3%) Thoracic and Cardiovascular Surgeon
Vol. 62
No. 7/2014
613
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis
Cheufou et al.
Fig. 3 Overall survival curve. Lobectomy versus segmentectomy.
Fig. 4 Overall survival curve: Age; under 55 years versus over 55 years.
had atelectasis requiring bronchoscopy, and seven (19%) had prolonged air leak. In addition, arrhythmia was noted in one (3%) patient. Beyond all of this, there was one case of pulmonary embolism (3%), one case of empyema (3%), and one case of bleeding with the need for surgical revision (3%). The follow-up was completed for all 37 patients with a median follow-up of 17.3 months (range: 2–69). Currently, three patients are alive without any evidence of a recurrent disease. The overall survival was 62 and 24% after 1 and 2 years. Univariate analysis revealed that neither age, sex, tumor histology, primary location, type of resection, adjuvant therapy, nor nodal status significantly affected survival (►Fig. 4).
fore lung surgery. No instance of cerebral recurrence was found in this series. One report on recurrent cancer in the brain after craniotomy and whole brain radiotherapy indicates that additive procedures for cerebral local control have become an important part of the therapy.1 Even though a conventional particle accelerator can be used to deliver a boost after whole brain radiotherapy in selected patients, the benefit is not significant enough and the results are not satisfying.12 Moreover, the risk of dementia increases with high radiation doses. All patients of the sample used in this study underwent surgery without positron emission tomography (PET)/CT. A mediastinoscopy was performed on 26 (70%) of the patients. It appears that the number of mediastinoscopies can be reduced by using PET scans or endobronchial ultrasound as substitutes. At the time of this study, neither of these diagnostic tools had been available at the institution. In contrast to that, these tools are now part of the standard clinical evaluation of all patients with bronchial carcinoma. In this series, a large number of patients had tumors categorized as N1 (27%) and N2 (28%). However, there was no statistical difference in survival compared with the other patients. This observation was also made by Burt and associates, who found no difference in survival between patients with stages I and II NSCLC compared with patients with stages III and IV disease.12 They also found that one patient with a stage N1 disease was still alive 5 years after lung resection, and another patient with a stage N2 disease was still alive 32 months after lung resection. Of the 11 patients in stage N2, we found that 8 of them had paraesophageal lymph node metastases which could not be detected with standard mediastinoscopy. Only three patients were subcarinal in stage N2. Of these, two did not undergo mediastinoscopy due to unsuspicious lymph nodes in the CT scan. Rossi et al compared the outcome of patients after the resection of both tumor sites and whole brain radiotherapy to that of patients receiving resection of only the cranial tumor without resection of NSCLC.13 They found that the 1-year survival of patients without resection of NSCLC was 15%; all
Discussion Approximately 15 to 20% of all patients with NSCLC develop brain metastases during the course of their disease.2,3 Without any treatment, the median survival time from the first diagnosis of brain metastases is approximately 1 to 6 months.4,7 The best approach to manage a single cerebral metastasis differs depending on the location, primary histology, and general condition of the patient. Corticosteroid administration in patients with brain metastases offers a rapid improvement of the neurological symptoms but does not prolong survival beyond 3 months.8 Some authors treat cerebral recurrence successfully with pemetrexed. Here, the blood– brain barrier, which normally protects CNS from cytotoxic agents, becomes less functional in the presence of brain metastases.1 We did not receive patients with small cell lung cancer. It appears that after cerebral metastasectomy with the detection of small cell lung cancer, the patients were embedded in nonsurgical concepts and not considered for surgery. The results of randomized trials revealed that the survival after craniotomy plus a whole brain radiation therapy for a single cerebral metastasis was significantly better than the survival after brain radiotherapy alone.9–11 In the presented study, all patients underwent cerebral metastasectomy beThoracic and Cardiovascular Surgeon
Vol. 62
No. 7/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
614
Surgery of Primary Lung Cancer with Oligometastatic M1b Synchronous Single Brain Metastasis References
1 Ochi N, Yamane H, Yamagishi T, Takigawa N. Continuous peme-
2
3
4
5
6
7
8 9
10
11
12
Conclusion Combined surgical resection of both tumor sites in patients with NSCLC and single brain metastases can be implemented with low risks of mortality or morbidity and with the chance of prolonged survival. The described findings indicate that whenever possible, a surgical approach should be considered for well-evaluated patients.
13
14
15 16
Conflict of Interest There are no conflicts of interest to report.
615
trexed treatment for brain metastasis in non-small cell lung cancer —a report of two cases. Lung Cancer 2013;80(1):111–113 Kawabe T, Phi JH, Yamamoto M, Kim DG, Barfod BE, Urakawa Y. Treatment of brain metastasis from lung cancer. Prog Neurol Surg 2012;25:148–155 Billing PS, Miller DL, Allen MS, Deschamps C, Trastek VF, Pairolero PC. Surgical treatment of primary lung cancer with synchronous brain metastases. J Thorac Cardiovasc Surg 2001;122(3):548–553 Knights EM Jr. Metastatic tumors of the brain and their relation to primary and secondary pulmonary cancer. Cancer 1954;7(2): 259–265 Figlin RA, Piantadosi S, Feld R. Intracranial recurrence of carcinoma after complete surgical resection of stage I, II, and III non-small-cell lung cancer. N Engl J Med 1988;318(20):1300–1305 Magilligan DJ Jr, Duvernoy C, Malik G, Lewis JW Jr, Knighton R, Ausman JI. Surgical approach to lung cancer with solitary cerebral metastasis: twenty-five years’ experience. Ann Thorac Surg 1986; 42(4):360–364 Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322(8):494–500 Ruderman NB, Hall TC. Use of glucocorticoids in the palliative treatment of metastatic brain tumors. Cancer 1965;18:298–306 Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998;280(17):1485–1489 Vecht CJ, Haaxma-Reiche H, Noordijk EM, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 1993;33(6):583–590 Lévy A, Chargari C, Lamproglou I, Mazeron JJ, Krzisch C, Assouline A. Whole brain radiation with supplementary boost for patients for unique brain metastasis from a primitive lung cancer [in French]. Cancer Radiother 2011;15(5):426–429 Burt M, Wronski M, Arbit E, Galicich JH; Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff. Resection of brain metastases from non-small-cell lung carcinoma. Results of therapy. J Thorac Cardiovasc Surg 1992;103(3):399–410, discussion 410–411 Rossi NP, Zavala DC, VanGilder JC. A combined surgical approach to non-oat-cell pulmonary carcinoma with single cerebral metastasis. Respiration 1987;51(3):170–178 Read RC, Boop WC, Yoder G, Schaefer R. Management of nonsmall cell lung carcinoma with solitary brain metastasis. J Thorac Cardiovasc Surg 1989;98(5 Pt 2):884–890, discussion 890–891 Richards P, McKISSOCK W. Intracranial metastases. BMJ 1963; 1(5322):15–18 Griffioen GH, Toguri D, Dahele M, et al. Radical treatment of synchronous oligometastatic non-small cell lung carcinoma (NSCLC): patient outcomes and prognostic factors. Lung Cancer 2013;82(1):95–102
Thoracic and Cardiovascular Surgeon
Vol. 62
No. 7/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
died within 2 years. Patients with the resection of both sites plus the whole brain radiotherapy displayed a 1-year survival rate of 35%, and the subsequent 2-year survival rate was 25%.14 In this series, the overall survival at 1 and 2 years was at least similar or even better. The hospital mortality rate was 2% in another series and all patients surviving for more than 2 years were patients who underwent resection of both tumor sites.15 In this series, the 30-day mortality was 0%, similar to that found by Read.14 This observation confirms that the approach of surgically treating both sites can be used safely in well-selected patients. The identification of prognostic factors was not within the scope of this study. All in all, there is evidence that recommends the complete resection of both tumor sites for patients with single brain metastases and resectable tumor in the lung. The presented study revealed that neither survival nor the disease-free interval was connected to age, primary tumor or lymph node status, tumor histology, size, side, or the type of pulmonary resection. Limitations of this study can be seen in the retrospective study design and the restriction on a single-center source of experience. Furthermore, the application of pre- or postoperative chemotherapy could not be analyzed with respect to remission, nor could we analyze the pattern of recurrence in those patients who died. Some patients are reported to have died within a relatively short time span after the monitored period of 2 years. It appears likely that micrometastases which were undetectable at the time of diagnosis could have been an important factor in the death of these patients.16
Cheufou et al.
Copyright of Thoracic & Cardiovascular Surgeon is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
