A prognostic score from a multicentric retrospective analysis of patients affected by sarcoma with metachronous lung metastases undergoing metastasectomy.

BACKGROUND: Despite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. METHODS: A retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in six research institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. RESULTS: A total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). CONCLUSION: The proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

Chemosensitivity of Lung Metastatic High-Grade Synovial Sarcoma.

Background: Synovial sarcoma is a relatively chemosensitive type of soft tissue sarcoma and it often metastasizes to the lung. We investigated the role of adjuvant chemotherapy in patients with high-grade synovial sarcoma at their first lung metastasectomy (LMTS). Methods: Forty-six HGSS patients had their first LMTS at our institute (Rizzoli Orthopedic Hospital, Bologna, Italy) between 2000 and 2020. We divided them into two groups: (1) those undergoing adjuvant chemotherapy (n = 24) and (2) those not receiving adjuvant chemotherapy (n = 22). The primary outcome was a median survival at 32.5 (IQR 18.0-82.7) median follow-up. The disease-free interval was calculated at time zero (DFI0, interval between the diagnosis of the primary tumor and the first CT-diagnosed lung metastasis) and at any further lung relapse (DFI1-3). T0 was defined as the time at first LMTS and T1-T3 referred to the time of further metastasectomy. Results: Freedom from SS-specific mortality at 60 months was significantly higher in patients without chemotherapy (50.0% (33.0-76.0%) vs. 20.8% (9.55%-45.4%), p = 0.01). Chemotherapy was associated with a higher risk of SS-specific mortality at multivariable Cox regression (HR 2.8, p = 0.02). Furthermore, DFI0 ≤ 6 months, female sex, age > 40 years, and primary tumor > 10 cm increased the risk of death by about four, six, >three, and >five times, respectively. Conclusions. Adjuvant chemotherapy did not show any advantage in terms of freedom from SS-specific mortality in HGSS patients. Further larger studies are necessary to confirm our findings.

Predictors of lung recurrence and disease-specific mortality after pulmonary metastasectomy for soft tissue sarcoma.

BACKGROUND: We identified prognostic factors in a 30-year series of STS treated at a single Institution, using an advanced statistical approach. METHODS: From June 1988 to July 2019, 164 patients were referred to Rizzoli Orthopedic Hospital, Bologna, Italy) for STS lung metastasectomy (LMTS). The endpoints were lung metastasis recurrence (LMR) and lung metastasis-specific mortality (LMSM). The analysis included directed acyclic graphs, cubic splines, and a competing risk model in order to minimize bias. RESULTS: The 10- and 15- year LMR cumulative incidence were 0.77 (0.76-0.78) whereas 10- and 15- year freedom from LMSM were 0.60 [0.51-0.70] and 0.56 [0.47-0.67], respectively. The malignant peripheral nerve sheath tumor (MPNST) histotype (SHR 4.12 [2.05-8.27]), a disease-free interval (DFI) up to 68 months (HR from 2 [1.7-2.2] to 1.5 [1.1-1.9]) and a LM size ≥4 mm (3.1 [2.1-4.4]) predicted LMR. Myxofibrosarcoma (HR 2.52[1.64-3.86]), synovial sarcoma (2.53[1.22-5.23]), adjuvant chemotherapy (2.01[1.11-3.61]), DFI between 2 months and 20 months (HR from 1.5 [1.1-2.3] to 1.3 [1.1-1.7] and primary tumor size a primary tumor size comprised between 3.6 cm and 10 cm predicted LMSM. A sharp increase in LMSM was observed with a tumor size from ≥20 cm. CONCLUSIONS: Our analysis corrected by potential confounders allowed us to identify specific histotypes and DFI intervals as predictors of both LMR and LMSM. Tumor size adjuvant chemotherapy adversely affected LM-related survival. Our findings need to be confirmed by larger randomized studies.

Primary lung adenocarcinoma in three adolescent patients affected by bone sarcomas.

Pediatric primary lung carcinomas are extremely rare. Apart from known associations with congenital adenomatoid malformations, cases of primary lung adenocarcinomas after prolonged treatments of pediatric malignancy have been reported. We describe the morphological and molecular features of three cases of lung adenocarcinoma developed in adolescents aged 8 to 17 years during progression of their bone osteosarcoma or Ewing sarcomas. The morphological features overlapped those of adult lung adenocarcinoma including in situ, minimally invasive, and invasive forms. EGFR gene mutations were found in all three cases by targeted next-generation sequencing. The two patients with Ewing sarcoma had no progression of their lung cancer and no further progression of the metastatic bone tumor after additional chemo- and radio-therapy. Conversely, the osteosarcoma patient refused further treatments after thoracic surgery for metastatic osteosarcoma and locally advanced adenocarcinoma and died 2 years later of widespread distant metastases. Our results indicate that primary lung cancer might originate in pediatric patients during prolonged adjuvant therapies for primary bone neoplasm, and this possibility should be considered in the presence of suspected lung disease progression to correctly monitor the primary tumor evolution and define the appropriate therapeutic strategy at each time point. If appropriately treated, second primary lung cancer may not affect the patients' prognosis. The pathogenetic mechanisms of these rare lung adenocarcinomas are not clear, but the presence of EGFR mutations in all three cases indicates an oncogene addiction of the lung tumor, rather than a direct cancerogenic effect of the sarcoma-related treatment.

Chondroblastoma's Lung Metastases Treated with Denosumab in Pediatric Patient.

Chondroblastoma is a rare benign chondrogenic tumor that occurs in skeletally immature patients between ages 10 and 20 years old. In literature are reported few cases of lung metastases, mainly occurred after surgery or local recurrences. There is no evidence on the pathogenesis of lung metastasis, as well as pulmonary disease course. Few treatments for metastases with aggressive behavior were based on chemotherapy regimen employed in other sarcoma with no results or not satisfying ones. Denosumab is approved for treatment of giant cell tumors and it is under investigation for other giant cell-rich bone tumors. Here, we report a case of a 16-year-old male chondroblastoma of the left humerus with bilateral lung metastases at presentation and progressing during follow-up, treated with denosumab for almost 2 years. We confirm that denosumab treatment can be effective in controlling chondroblastoma metastasis and it has been a safe procedure in an adolescent patient.

Outcome of lung metastases due to bone giant cell tumor initially managed with observation.

BACKGROUND: The outcomes of patients with lung metastases from giant cell tumor of bone (GCTB) vary from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management approach for patients with lung metastases from GCTB, we evaluated the outcomes of patients who were initially managed by observation. METHODS: We retrospectively reviewed the data of 22 patients with lung metastases from histologically confirmed GCTB who received observation as a first-line treatment approach. The median follow-up period was 116 months. RESULTS: Disease progression occurred in 12 patients (54.5%). The median interval between the discovery of lung metastases and progression was 8 months. Eight patients underwent metastasectomy following initial observation. The median interval between the discovery of lung metastases and treatment by metastasectomy was 13.5 months. None of the patients experienced spontaneous regression. Of the 22 patients, 36.4% needed a metastasectomy, and 9.1% required denosumab treatment during the course of the follow-up period. Disease progression occurred in 45.5% of the 11 patients with lung nodules ≤ 5 mm, while all five of the patients with lung nodules > 5 mm experienced disease progression. Progression-free survival was significantly worse in the group with lung nodules > 5 mm compared to the group with lung nodules ≤ 5 mm (p = 0.022). CONCLUSIONS: Observation is a safe first-line method of managing patients with lung metastases from GCTB. According to radiological imaging, approximately half of the patients progressed, and approximately half required a metastasectomy or denosumab treatment. However, patients with lung nodules > 5 mm should receive careful observation because of the high rate of disease progression in this group.

Clinical and Radiologic Features Together Better Predict Lung Nodule Malignancy in Patients with Soft-Tissue Sarcoma.

We test the hypothesis that a model including clinical and computed tomography (CT) features may allow discrimination between benign and malignant lung nodules in patients with soft-tissue sarcoma (STS). Seventy-one patients with STS undergoing their first lung metastasectomy were examined. The performance of multiple logistic regression models including CT features alone, clinical features alone, and combined features, was tested to evaluate the best model in discriminating malignant from benign nodules. The likelihood of malignancy increased by more than 11, 2, 6 and 7 fold, respectively, when histological synovial sarcoma sub-type was associated with the following CT nodule features: size ≥ 5.6 mm, well defined margins, increased size from baseline CT, and new onset at preoperative CT. Likewise, in the case of grade III primary tumor, the odds ratio (OR) increased by more than 17 times when the diameter of pulmonary nodules (PNs) was >5.6 mm, more than 13 times with well-defined margins, more than 7 times with PNs increased from baseline CT, and more than 20 times when there were new-onset nodules. Finally, when CT nodule was ≥5.6 in size, it had well-defined margins, it increased in size from baseline CT, and when new onset nodules at preoperative CT were concomitant to residual primary tumor R2, the risk of malignancy increased by more than 10, 6, 25 and 28 times, respectively. The combination of clinical and CT features has the highest predictive value for detecting the malignancy of pulmonary nodules in patients with soft tissue sarcoma, allowing early detection of nodule malignancy and treatment options.

Lung Metastasectomy Improves Survival in Patients Affected by Grade 2 and 3 Chondrosarcoma.

AIMS: The aim of this retrospective study is to evaluate the role of pulmonary metastasectomy (PM) in patients affected by lung metastasis (LM) of grade 2 and 3 chondrosarcoma (CS). PATIENTS AND METHODS: The study included 61 patients affected by LM. Patients unfit for PM were treated with chemotherapy and radiotherapy. RESULTS: The patients' mean age was 51 years, ranging from 17 to 84 years; 44 (66.7%) patients had grade 2 CS, while 17 (25.8%) patients had grade 3 CS. Fifty-one patients presented multiple nodules: 44 of those cases were bilateral LM (72.1%). Twenty-nine (47.5%) patients underwent PM, whereas 32 (52.5%) patients underwent chemotherapy and stereotactic radiotherapy alone. At the final follow-up (average of 83 months, range 13-298), 47 (77.0%) patients had died of the disease. A better post-relapse survival rate was observed in patients who underwent PM (55.1 vs. 13.1% at 5-year follow-up, p < 0.001) and in patients with unilateral LM (60.4 vs. 25.6% at 5-year follow-up, p = 0.016). The number of LM also played a prognostic role. CONCLUSIONS: Until significant improvements in chemotherapy can be made, PM can be a valid option in the attempt to improve post-metastatic survival.

Survival after second and subsequent recurrences in osteosarcoma: a retrospective multicenter analysis.

PURPOSE: Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. METHODS: This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. RESULTS: Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. CONCLUSIONS: This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

Erratum to: Osteosarcoma follow-up: chest X-ray or computed tomography?

[This corrects the article DOI: 10.1186/s13569-017-0067-5.].

Survival after Second and Subsequent Recurrences in Osteosarcoma: A Retrospective Multicenter Analysis.

Purpose Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. Methods This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. Results Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. Conclusions This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

Osteosarcoma follow-up: chest X-ray or computed tomography?

BACKGROUND: In patients with relapsed osteosarcoma, the surgical excision of all metastases, defined as second complete remission (CR-2), is the factor that mainly influences post-relapse survival (PRS). Currently a validated follow-up policy for osteosarcoma is not available, both chest X-ray and computed tomography (CT) are suggested for lung surveillance. The purpose of this study is to evaluate whether the type of imaging technique used for chest surveillance, chest X-ray or CT, influenced the rate of CR-2 and prognosis in patients with recurrent osteosarcoma. METHODS: Patients up to 40 years with extremity osteosarcoma enrolled in consecutive clinical trials and treated at the Rizzoli Institute from 1986 to 2009 were identified. Only patients who had lung metastases alone as first pattern of recurrence were considered for the analysis. The rate of CR-2, overall survival (OS) and PRS were the end-points of the study. RESULTS: The median follow-up was 47 months (1-300), 215 patients were eligible. Lung metastases were detected by chest X-ray in 100 (47%) patients, by CT in 112 (52%) and by symptoms in 3 (1%). CR-2 rate was 60% for patients followed by X-rays and 88% for those followed by CT (p < .0001). 5-year PRS was 30% (95% CI 21-39) in the X-ray group and 49% (95% CI 39-59) in the CT group (p = .0004). 5-year OS was 35% (95% CI 26-44) in the X-ray group and 60% (95% CI 51-70) in the CT group (p = .004). CONCLUSIONS: A follow-up strategy with chest CT leads to a higher rate of CR-2 and significantly improves PRS and OS in osteosarcoma, compared to chest X-ray.

The many faces of pulmonary metastases of osteosarcoma: Retrospective study on 283 lesions submitted to surgery.

OBJECTIVE: CT is the recommended technique for the detection of pulmonary metastases in patients affected by osteosarcoma, though claimed to show several limits compared to manual palpation. We retrospectively analyzed CT features of suspected lesions submitted to surgery to address its current accuracy and to investigate criteria for predicting histology. MATERIALS AND METHODS: CT scans of 70 patients submitted to thoracotomy between 2007-2013 were reviewed. Overall, 123 thoracotomies were performed and 283 lesions seen on CT were resected. Shape, size, presence and type of calcification, evolution of each lesion were analyzed. Number and histology of nodules detected at thoracotomy were recorded and compared to CT data. RESULTS: 234/283--82.7% Lesions were metastases; 143--61.1% were calcified; most metastases were nodular (201/234--85.9%), but in 33/234--14.1% other findings were detected (striae, consolidations, pleural plaques/masses, cavitations, ground glass opacities, irregular shapes, halo sign). Malignant lesions were more frequently calcified, larger, with progression over time--p<0.0001. Manual palpation identified 314 lesions, 248 metastatic--79.0%: CT missed 31/314--9.9% lesions, whereof 14/31--45.2% were metastases. CONCLUSIONS: Though most lesions are nodular and calcified, up to 40% are not calcified and atypical findings are not uncommon (14.1%). The identification of the atypical radiological presentation of metastases could be the key for improving CT accuracy.

Stereotactic Radiotherapy in the Treatment of Lung Metastases from Bone and Soft-tissue Sarcomas.

BACKGROUND: The purpose of this study was to evaluate local control and toxicity in a group of patients treated with stereotactic body radiotherapy (SBRT) for lung metastases (LM) from bone and soft tissue sarcomas. PATIENTS AND METHODS: From October 2010 to July 2014, patients with LM from sarcomas not suitable for surgery were treated with daily cone-beam computed tomography-guided SBRT. The dose administered ranged from 30 to 60 Gy in 3-8 fractions. Acute and late toxicity were scored according to Common Terminology Criteria for Adverse Events version 4.0. RESULTS: A total of 24 patients with 68 LM from sarcomas were treated with SBRT. The median follow-up after SBRT was 17 months (range=11-51 months). Two-year actuarial lesion local control and overall survival were 85.9% and 66.4%, respectively. No G3 or greater acute and late toxicities were observed. CONCLUSION: SBRT is a safe and effective treatment for LM from sarcoma and might be used as an alternative option in patients unfit for surgery.

Designing neural networks for modeling biological data: a statistical perspective.

In this paper, we propose a strategy for the selection of the hidden layer size in feedforward neural network models. The procedure herein presented is based on comparison of different models in terms of their out of sample predictive ability, for a specified loss function. To overcome the problem of data snooping, we extend the scheme based on the use of the reality check with modifications apt to compare nested models. Some applications of the proposed procedure to simulated and real data sets show that it allows to select parsimonious neural network models with the highest predictive accuracy.

A case of lung metastasis in myxoinflammatory fibroblastic sarcoma: analytical review of one hundred and thirty eight cases.

PURPOSE: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue tumour first identified at the end of the 1990s. This study presents our experience and literature reviews focusing on risk of recurrence. METHODS: Rizzoli Orthopaedic Institute database and literature were searched for patients with MIFS observed from 1997 to 2012. Data were analysed in a new database. RESULTS: Five patients underwent surgery at our institute, and 133 cases were retrieved from the literature. Not all clinicopathological data were available: 76/138 were men (55%), median age was 45 [interquartile range (IQR) 34-56] years, median tumour size was three (IQR two to five) centimetres. Common sites of occurrence were hand (24%), fingers (23%) and foot (20%). Pain was present at diagnosis in 14/82 patients (17%), with a median duration of seven (IQR three to 12) months. Surgery was performed for a suspected benign tumour in 88 patients (74%). Resection was incomplete in 45/71 cases (63%); re-excision was performed in 32/45 (71%). At a median follow-up of 26 months, 26/118 patients (22%) developed recurrent disease; median time to recurrence was 15 months (IQR seven to 26). Actuarial relapse-free survival (RFS) at one, three and five years was 93%, 72% and 67%, respectively. At univariate analysis, only symptom duration of six months or less was significantly associated with a worse RFS (p = 0.046). Metastatic disease to lymph nodes and/or lungs was observed in four patients (3%). CONCLUSIONS: Clinicopathological findings confirm the low-grade nature of MIFS. However, local recurrence occurs, and patients may be affected by aggressive forms with a potential for distant metastases. Follow-up is strongly advised.

High grade osteosarcoma of the extremities metastatic to the lung: long-term results in 323 patients treated combining surgery and chemotherapy, 1985-2005.

BACKGROUND: Approximately one-third of patients with localized osteosarcoma at presentation relapse as well as about three-fourths of the patients with metastases at diagnosis, about 90% of relapses are lung metastases. The role of lung metastasectomy remains to be determined. PATIENTS: and methods: Three hundred and twenty three patients, 88 with resectable lung metastases at diagnosis and 235 with localized disease at presentation who relapsed with lung metastases were treated. RESULTS: A total of 498 lung surgeries and 607 thoracotomies were performed. The 5 year overall survival was 37%. Final outcome was significantly related to presence or absence of metastasis, time of first relapse and presence of local recurrences. According to stage of the disease, the rate of a 5 year event-free survival (EFS) was 36% for patients with localized disease who later relapsed and 9% for patients with resectable lung metastases at presentation (p<0.0001). However, there were no differences in EFS between patients who underwent two or three thoracotomies and patients who had four or five thoracotomies (7.5 vs 18.7%, p=0.29). CONCLUSIONS: In patients with recurrent resectable pulmonary metastases from high grade osteosarcoma treated with adjuvant or neoadjuvant chemotherapy, thoracotomy should always be considered regardless the number of previous lung relapses and the number of secondary pulmonary lesions.

Local and systemic control of Ewing's bone sarcoma family tumors of the ribs.

BACKGROUND: A retrospective analysis of the results and relapse pattern was evaluated in 34 patients with Ewing's family bone tumors (EFBT) treated at Rizzoli Institute with neoadjuvant chemotherapy between 1983 and 2003. OBJECTIVES: The aim of the study was to evaluate treatment strategy and compare our results with those obtained in other studies. METHODS: Local treatment in these patients was radiotherapy alone in 4 cases, surgery alone in 13 and surgery followed by radiotherapy in 17. RESULTS: Five-year event-free survival (EFS) was 44%, no different from that observed in another 558 patients with EFBT located in other sites treated in the same period with neoadjuvant chemotherapy protocols. Eighteen patients had a systemic relapse, followed by local relapse in two and one patient had a local relapse alone. EFS was significantly correlated to the time interval between onset symptoms and beginning of treatment and, in operated patients to histologic response to preoperative treatment. CONCLUSIONS: We conclude that EFBT of the ribs, when treated with neoadjuvant chemotherapy, have an outcome similar to that of patients with EFBT located in other sites.

"Bubble-like" lung metastases in osteosarcoma patients.

PURPOSE: Cavitation of pulmonary metastases have been reported by several authors either as a spontaneous phenomenon or as a consequence of chemotherapy. We present two cases, with this type of image in follow-up, and 20-45 months after the end of treatment. This was the first sign of pulmonary metastases. RESULTS: Two patients with osteogenic sarcoma developed radiological evidence of pulmonary "bubble-like" cavitation several years following completion of chemotherapy. In one patient the "bubble-like" cavitation transformed into a solid nodule. Both patients had surgical resections of all pulmonary lesions, and histology confirmed presence of viable osteosarcoma metastases. CONCLUSION: The two cases suggest that onset of "bubble-like" cavitation in lung parenchyma of osteosarcoma patients may be the first sign of pulmonary metastases.

High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions.

BACKGROUND AND METHODS: Between 1986 and 2001, 162 patients with extremity osteosarcoma and lung metastases at presentation, were treated by neoadjuvant chemotherapy, simultaneous resection of primary and, when feasible, secondary lesions followed by chemotherapy. RESULTS: After neoadjuvant chemotherapy, metastases disappeared in 14 patients, 16 were judged unresectable by both our thoracic surgeons, 132 had primary tumors and lung metastases removed simultaneously. Removal of lung metastases was complete in 123 and incomplete in 9. Histologically lesions were benign in 32 patients. For the 100 patients simultaneously operated with histologically proven lung metastases, 5-year event-free survival (EFS) was 18.9%; 27.4% for the 91 who had a complete resection of pulmonary lesions and entered remission as opposed to none for 9 patients who had incomplete removal of lung nodules. Among these 91, 5-year EFS was significantly higher for patients with monolateral compared to bilateral lesions (27.1% vs. 7.9%, P < 0.02) and when only one to three metastatic nodules were present (40.0% vs. 13.3%, P < 0.0001). CONCLUSIONS: These different results, demonstrate that our treatment had a reasonable survival outcome whereas other groups continue to have dismal prognosis. More efforts should be made to improve survival by identifying new active agents or novel approaches with cellular molecular targets.