- Email: [email protected]
Salvage Operation in Case of Oligometastatic Disease
Salvage Operation in Case of Oligometastatic Disease Nicolas Duchateau, BS, Erik Van Bouwel, MD, and Paul E. Van Schil, MD, PhD Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp; Department of Pulmonary Medicine, KLINA (Klinieken Noord-Antwerpen) Hospitals, Brasschaat; and Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Antwerp, Belgium
In general, prognosis of stage IV non-small cell lung cancer is poor, and treatment is mostly palliative. However, oligometastatic disease is currently recognized as a specific entity with a better prognosis. We report a patient where combined chemoradiotherapy and salvage surgery led to extraordinary long-term survival. (Ann Thorac Surg 2017;103:e409–11) Ó 2017 by The Society of Thoracic Surgeons
A
specific subset of stage IV non-small cell lung cancer is known as the oligometastatic state, which consists of patients with a limited number of metastases in limited organ sites. Salvage operations have rarely been reported in this particular situation. In June 2006, a 50-year-old male patient, with a 30 packyear history of smoking, presented with nonexerciserelated pain in the left leg. A lower limb roentgenogram showed an osteolytic process at the subtrochanteric region of the left femur, which was confirmed by magnetic resonance imaging (Fig 1). The lesion was highly suspicious for a metastatic focus. Chest computed tomography scanning revealed a 4-cm spiculated mass in the right upper lobe and an enlarged hilar lymph node suspicious for a primary bronchogenic carcinoma (Fig 2). Bronchoscopic biopsy specimens confirmed the diagnosis of primary necrotizing non-small cell lung cancer. Immunostaining was positive for cytokeratin 7 and negative for cytokeratin 20. There was no evidence for other distant metastases. Diagnosis of a primary lung carcinoma with a synchronous solitary metastatic bone lesion was made (cT2a N1 M1b). Because of the threat of fracture, the left femur was stabilized with an osteosynthetic plate and hip screws. Bone biopsy specimens confirmed a metastatic lesion. Postoperative consolidating radiotherapy to the femur was applied. Subsequently, to treat the right upper-lobe cancer, sequential chemoradiotherapy was administered consisting of 6 cycles of cisplatin-gemcitabine, followed by high-dose external radiotherapy. Follow-up with chest computed tomography scanning initially demonstrated stable disease. However, a positron emission tomography scan in December 2007, 17 months
Fig 1. Magnetic resonance image shows an osteolytic lesion in the left femur.
after treatment, revealed progressive growth at the right upper lobe (Fig 3). No other foci were present, and there was also no uptake in the left femur. The result of a cervical mediastinoscopy was negative, and a salvage right upper lobectomy with systematic lymph node dissection was performed in January 2008. Apart from pronounced fibrosis at the right upper lobe bronchus, there were no intraoperative technical difficulties. The patient’s postoperative recovery was uneventful, besides a surgical wound infection. Pathologic staging of the lung cancer was pT1b N1, and complete resection was obtained. No further treatment was given. More than 8 years postoperatively, the patient is alive without evidence of disease.
Comment In general, being diagnosed with stage IV lung cancer heralds a poor prognosis. However, there are subcategoric differences, with M1a (metastases within the
Accepted for publication Nov 4, 2016. Address correspondence to Dr Van Schil, Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem (Antwerp), Belgium; email: [email protected].
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier Inc.
Fig 2. Chest computed tomography scan demonstrates an irregular tumor in the right upper lobe. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.11.019
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CASE REPORT DUCHATEAU ET AL SALVAGE OPERATION FOR OLIGOMETASTASIS
Ann Thorac Surg 2017;103:e409–11
Fig 3. Follow-up positron emission tomography-computed tomography scans show an enlarging tumor in the right upper lobe.
chest cavity) having the best prognosis, with a median survival time of 11.5 months, which was demonstrated by a recent analysis from the International Association for the Study of Lung Cancer [1]. In addition, tumors with a single metastasis in a single organ had significantly better prognosis than those with multiple metastases in one or several organs, with a median survival time of 11.4 and 6.3 months, respectively. For this reason, a subcategory M1b is introduced in the eighth TNM classification consisting of a single metastasis in a single extrathoracic organ [1]. Multiple distant metastases or involvement of different extrathoracic sites will be categorized as M1c disease. Patients with oligometastatic disease and otherwise limited disease in the chest may benefit from aggressive local therapy to both the primary thoracic and metastatic site of disease, as shown in our patient [2]. Because of local progressive disease, a salvage operation could be performed because there were no signs of extrathoracic involvement. Long-term survival after primary tumor resection and metastasectomy for solitary brain or adrenal metastasis has been reported. However, outcome and predictive factors for survival after treatment for extracranial and extraadrenal solitary metastasis (such as bone metastasis) have not been clearly established. According to Salah and
colleagues [3], only mediastinal lymph node involvement is a poor prognostic factor. Whether the combination of induction chemotherapy and surgical resection for non-small cell lung cancer with a synchronous solitary metastasis is beneficial is not clear. In the only prospective but older trial, 23 patients were enrolled, and 10 patients underwent complete resection of the primary site and the solitary M1 site. Unfortunately, the chemotherapy used (mitomycinvinblastine-cisplatin) was not well tolerated due to toxicity. Moreover, N2 disease was present in 7 of the 14 patients (50%) who underwent resection of the primary tumor, which is an additional poor prognostic factor. Overall and disease-free survival rates were poor, with only 2 true 5-year survivors [4]. With current chemotherapeutic regimens or targeted therapies, sometimes in combination with radiotherapy, a better overall and disease-free survival can be anticipated if N2 involvement is also excluded. Patients with M1b disease, previously considered incurable, could now be treated with curative intent. These patients should be well selected to profit from an aggressive approach that subsequently can lead to longterm survival. To make more definitive recommendations, further prospective studies should be conducted.
Ann Thorac Surg 2017;103:e409–11
References 1. Eberhardt WE, Mitchell A, Crowley J, et al. The IASLC lung cancer staging project: proposals for the revision of the M descriptors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 2015;10: 1515–22. 2. National Comprehensive Cancer Network. 2016 NCCN clinical practice guidelines in oncology: non-small cell lung cancer (version 4.2016). Available at https://www.nccn.org/
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professionals/physician_gls/pdf/nscl.pdf. Accessed May 15, 2016. 3. Salah S, Tanvetyanon T, Abbasi S. Metastatectomy for extracranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases. Lung Cancer 2012;75:9–14. 4. Downey RJ, Ng KK, Kris MG, et al. A phase ii trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis. Lung Cancer 2002;38:193–7.
In general, prognosis of stage IV non-small cell lung cancer is poor, and treatment is mostly palliative. However, oligometastatic disease is currently recognized as a specific entity with a better prognosis. We report a patient where combined chemoradiotherapy and salvage surgery led to extraordinary long-term survival. (Ann Thorac Surg 2017;103:e409–11) Ó 2017 by The Society of Thoracic Surgeons
A
specific subset of stage IV non-small cell lung cancer is known as the oligometastatic state, which consists of patients with a limited number of metastases in limited organ sites. Salvage operations have rarely been reported in this particular situation. In June 2006, a 50-year-old male patient, with a 30 packyear history of smoking, presented with nonexerciserelated pain in the left leg. A lower limb roentgenogram showed an osteolytic process at the subtrochanteric region of the left femur, which was confirmed by magnetic resonance imaging (Fig 1). The lesion was highly suspicious for a metastatic focus. Chest computed tomography scanning revealed a 4-cm spiculated mass in the right upper lobe and an enlarged hilar lymph node suspicious for a primary bronchogenic carcinoma (Fig 2). Bronchoscopic biopsy specimens confirmed the diagnosis of primary necrotizing non-small cell lung cancer. Immunostaining was positive for cytokeratin 7 and negative for cytokeratin 20. There was no evidence for other distant metastases. Diagnosis of a primary lung carcinoma with a synchronous solitary metastatic bone lesion was made (cT2a N1 M1b). Because of the threat of fracture, the left femur was stabilized with an osteosynthetic plate and hip screws. Bone biopsy specimens confirmed a metastatic lesion. Postoperative consolidating radiotherapy to the femur was applied. Subsequently, to treat the right upper-lobe cancer, sequential chemoradiotherapy was administered consisting of 6 cycles of cisplatin-gemcitabine, followed by high-dose external radiotherapy. Follow-up with chest computed tomography scanning initially demonstrated stable disease. However, a positron emission tomography scan in December 2007, 17 months
Fig 1. Magnetic resonance image shows an osteolytic lesion in the left femur.
after treatment, revealed progressive growth at the right upper lobe (Fig 3). No other foci were present, and there was also no uptake in the left femur. The result of a cervical mediastinoscopy was negative, and a salvage right upper lobectomy with systematic lymph node dissection was performed in January 2008. Apart from pronounced fibrosis at the right upper lobe bronchus, there were no intraoperative technical difficulties. The patient’s postoperative recovery was uneventful, besides a surgical wound infection. Pathologic staging of the lung cancer was pT1b N1, and complete resection was obtained. No further treatment was given. More than 8 years postoperatively, the patient is alive without evidence of disease.
Comment In general, being diagnosed with stage IV lung cancer heralds a poor prognosis. However, there are subcategoric differences, with M1a (metastases within the
Accepted for publication Nov 4, 2016. Address correspondence to Dr Van Schil, Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem (Antwerp), Belgium; email: [email protected].
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier Inc.
Fig 2. Chest computed tomography scan demonstrates an irregular tumor in the right upper lobe. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.11.019
e410
CASE REPORT DUCHATEAU ET AL SALVAGE OPERATION FOR OLIGOMETASTASIS
Ann Thorac Surg 2017;103:e409–11
Fig 3. Follow-up positron emission tomography-computed tomography scans show an enlarging tumor in the right upper lobe.
chest cavity) having the best prognosis, with a median survival time of 11.5 months, which was demonstrated by a recent analysis from the International Association for the Study of Lung Cancer [1]. In addition, tumors with a single metastasis in a single organ had significantly better prognosis than those with multiple metastases in one or several organs, with a median survival time of 11.4 and 6.3 months, respectively. For this reason, a subcategory M1b is introduced in the eighth TNM classification consisting of a single metastasis in a single extrathoracic organ [1]. Multiple distant metastases or involvement of different extrathoracic sites will be categorized as M1c disease. Patients with oligometastatic disease and otherwise limited disease in the chest may benefit from aggressive local therapy to both the primary thoracic and metastatic site of disease, as shown in our patient [2]. Because of local progressive disease, a salvage operation could be performed because there were no signs of extrathoracic involvement. Long-term survival after primary tumor resection and metastasectomy for solitary brain or adrenal metastasis has been reported. However, outcome and predictive factors for survival after treatment for extracranial and extraadrenal solitary metastasis (such as bone metastasis) have not been clearly established. According to Salah and
colleagues [3], only mediastinal lymph node involvement is a poor prognostic factor. Whether the combination of induction chemotherapy and surgical resection for non-small cell lung cancer with a synchronous solitary metastasis is beneficial is not clear. In the only prospective but older trial, 23 patients were enrolled, and 10 patients underwent complete resection of the primary site and the solitary M1 site. Unfortunately, the chemotherapy used (mitomycinvinblastine-cisplatin) was not well tolerated due to toxicity. Moreover, N2 disease was present in 7 of the 14 patients (50%) who underwent resection of the primary tumor, which is an additional poor prognostic factor. Overall and disease-free survival rates were poor, with only 2 true 5-year survivors [4]. With current chemotherapeutic regimens or targeted therapies, sometimes in combination with radiotherapy, a better overall and disease-free survival can be anticipated if N2 involvement is also excluded. Patients with M1b disease, previously considered incurable, could now be treated with curative intent. These patients should be well selected to profit from an aggressive approach that subsequently can lead to longterm survival. To make more definitive recommendations, further prospective studies should be conducted.
Ann Thorac Surg 2017;103:e409–11
References 1. Eberhardt WE, Mitchell A, Crowley J, et al. The IASLC lung cancer staging project: proposals for the revision of the M descriptors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 2015;10: 1515–22. 2. National Comprehensive Cancer Network. 2016 NCCN clinical practice guidelines in oncology: non-small cell lung cancer (version 4.2016). Available at https://www.nccn.org/
CASE REPORT DUCHATEAU ET AL SALVAGE OPERATION FOR OLIGOMETASTASIS
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professionals/physician_gls/pdf/nscl.pdf. Accessed May 15, 2016. 3. Salah S, Tanvetyanon T, Abbasi S. Metastatectomy for extracranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases. Lung Cancer 2012;75:9–14. 4. Downey RJ, Ng KK, Kris MG, et al. A phase ii trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis. Lung Cancer 2002;38:193–7.