Impact of Intraoperative Molecular Imaging after Fluorescent-Guided Pulmonary Metastasectomy for Sarcoma.

BACKGROUND: Intraoperative molecular imaging (IMI) has been shown to improve lesion detection during pulmonary sarcomatous metastasectomy. Our goal in this study was to evaluate whether data garnered from IMI-guided resection of pulmonary sarcoma metastasis translate to improved patient outcomes. STUDY DESIGN: Fifty-two of 65 consecutive patients with a previous history of sarcomas found to have pulmonary nodules during screening were enrolled in a nonrandomized clinical trial. Patients underwent TumorGlow the day before surgery. Data on patient demographics, tumor biologic characteristics, preoperative assessment, and survival were included in the study analysis and compared with institutional historical data of patients who underwent metastasectomy without IMI. p values < 0.05 were considered significant. RESULTS: IMI detected 42 additional lesions in 31 patients (59%) compared with the non-IMI cohort where 25% percent of patients had additional lesions detected using tactile and visual feedback only (p < 0.05). Median progression-free survival (PFS) for patients with IMI-guided pulmonary sarcoma metastasectomy was 36 months vs 28.6 months in the historical cohort (p < 0.05). IMI-guided pulmonary sarcoma metastasectomy had recurrence in the lung with a median time of 18 months compared with non-IMI group at 13 months (p < 0.05). Patients with synchronous lesions in the IMI group underwent systemic therapy at a statistically higher rate and tended to undergo routine screening at shorter interval. CONCLUSIONS: IMI identifies a subset of sarcoma patients during pulmonary metastasectomy who have aggressive disease and informs the medical oncologist to pursue more aggressive systemic therapy. In this setting, IMI can serve both as a diagnostic and prognostic tool without conferring additional risk to the patient.

Near-infrared intraoperative imaging for minimally invasive pulmonary metastasectomy for sarcomas.

BACKGROUND: Complete pulmonary metastasectomy for sarcoma metastases provides patients an opportunity for long-term survival and possible cure. Intraoperative localization of preoperatively identified metastases and identification of occult lesions can be challenging. In this trial, we evaluated the efficacy of near-infrared (NIR) intraoperative imaging using second window indocyanine green during metastasectomy to identify known metastases and to detect occult nodules. METHODS: Thirty patients with pulmonary nodules suspicious for sarcoma metastases were enrolled in an open-label, feasibility study (NCT02280954). All patients received intravenous indocyanine green (5 mg/kg) 24 hours before metastasectomy. Patients 1 through 10 (cohort 1) underwent metastasectomy via thoracotomy to assess fluorescence patterns of nodules detected by traditional methods (preoperative imaging and intraoperative visualization/bimanual palpation). After confirming reliability within cohort 1, patients 11 through 30 (cohort 2) underwent video-assisted thoracic surgery metastasectomy with NIR imaging. RESULTS: In cohort 1, 14 out of 16 preoperatively identified pulmonary metastases (87.5%) displayed tumor fluorescence. Nonfluorescent metastases were deeper than fluorescent metastases (2.1 cm vs 1.3 cm; P = .03). Five out of 5 metastases identified during thoracotomy displayed fluorescence. NIR imaging identified 3 additional occult lesions in this cohort. In cohort 2, 33 out of 37 known pulmonary metastases (89.1%) displayed fluorescence. Nonfluorescent tumors were deeper than 2.0 cm (P = .007). NIR imaging identified 24 additional occult lesions. Of 24 occult lesions, 21 (87.5%) were confirmed metastases and the remaining 3 nodules were lymphoid aggregates. CONCLUSIONS: NIR intraoperative imaging with indocyanine green (5 mg/kg and 24 hours before surgery) localizes known sarcoma pulmonary metastases and identifies otherwise occult lesions. This approach may be a useful intraoperative adjunct to improve metastasectomy.

Management of liver metastases of gastrointestinal stromal tumors (GIST).

INTRODUCTION: Liver metastases (LM) are crucial prognostic manifestation of gastrointestinal stromal tumors (GIST). With the advent of tyrosine kinase inhibitors (TKI), management of metastatic GIST has radically changed. Long clinical follow-up provides an increased proportion of GIST patients with LM who are candidates for potentially curative therapy. MATERIAL AND METHODS: Patients who underwent treatment for liver metastases of GIST between 2000-2009 in our department were included in the study. Mean follow-up was 84 months (range 40-145) months. In retrospective analysis we investigated clinical, macro-/microscopic and immunohistochemical criteria, surgical, interventional and TKI therapy as well. RESULTS: In 87 GIST-patients we identified 25 (29%) patients with metastatic disease. Of these, 12 patients (14%) suffered from LM with a mean age of 60.5 (range, 35-75) years. Primary GIST were located at stomach (n = 4, 33%) or small intestine (n = 8, 67%); all of them expressed CD117 and/or CD34. LM were multiple (83%), distributed in both lobes (67%). They were detected synchronously with primary tumor in 33% and metachronously in 77%. All patients with liver involvement were considered to treatment with TKI. LM were resected (R0) in 4 patients (33%). In recurrent (2/4) and TKI resistant cases, interventional treatment (radiofrequency ablation) and TKI escalation were carried out. During a median follow-up of 84 months (range 30-152), 2 patients died (16.5%) for progressive disease and one patient for other reasons. Nine patients (75%) were alive. CONCLUSION: Treatment of LM from GIST needs a multimodal approach. TKI-therapy is required at any case. In case of respectability, surgery must be carried out. In unresectable cases or recurrent/progressive disease, interventional treatment or TKI escalation should be considered. Therefore, these patients need to be treated in experienced centres, where multimodal approaches are established.

Pulmonary metastasectomy: a multivariate analysis of 440 patients undergoing complete resection.

Surgical resection is currently a standard approach for isolated lung metastases from different primary tumours. The aim of the present analysis is to evaluate the outcome of patients submitted to complete resection of pulmonary metastases and to determine prognostic factors for long-term survival. A group of 440 consecutive patients previously diagnosed with primary malignant solid tumours and submitted to complete surgical resection of lung nodules with suspected or diagnosed metastatic lesion were retrospectively reviewed. The average follow-up time was 43.2 months (range: 0-192) and the 60-month O.S. was 43.7%. Univariate analysis: patients with adenocarcinoma presented the highest 5-year survival rates (53.4%, P = 0.0001); DFI >36 months (P < 0.0001), number of nodules on CT scan (P = 0.0052), number of malignant nodules resected (P = 0.0252) and the size of the largest resected nodule (P < 0.0001) were also significant. Multivariate analysis: number of malignant nodules resected (P = 0.01), size of the largest nodule resected (P = 0.001), DFI >36 months (P < 0.001) and histology of the primary tumour (P = 0.017) had significant impact on survival. The benefit of such an aggressive surgical approach is only limited to selected subgroups of patients. The decision to consider a patient for resection of metastastic disease should include factors beyond the feasibility of complete removal.

Resultados de la metastasectomía pulmonar por osteosarcoma en niños (1985 a 2005) / Results of lung metastasectomy due to osteosarcoma in children (1985-2005)

En Cuba la incidencia real de la metastasectomía pulmonar en niños con diagnóstico anatomopatológico de osteosarcoma no es bien conocida. Describir los resultados de esta operación en los pacientes pediátricos operados en nuestro servicio en un período de 20 años fue el objetivo de este trabajo. Fueron operados 19 pacientes del total de 145 atendidos, entre los cuales fueron los varones en edades cercanas a la adolescencia a quienes con mayor frecuencia se practicó la metastasectomía pulmonar. Hubo un predominio de metástasis única; el pulmón más afectado fue el derecho, y por tanto, fueron más frecuentes los abordajes sobre ese hemitórax. La toracotomía vertical axilar derecha (técnica de Bordonne) y la metastasectomía en cuña fueron las técnicas más utilizadas. Pudimos observar, mediante métodos estadísticos y tablas de Kaplan Meier para sobrevida libre de eventos y la sobrevida global, que hubo una diferencia significativa en cuanto a la distribución de los tiempos y una alta morbilidad y mortalidad a pesar de la metastasectomía(AU)

In Cuba the real incidence of lung metastasectomy in children with anatomopathological diagnosis of osteosarcoma is not well known. The objective of this paper was to describe the results of this surgical procedure in pediatric patients operated on in our service in a period of 20 years. 19 patients of the total of 145 that received attention underwent surgery. Lung mastectomy was more frequent among males near the adolescence. There was a predominance of unique metastasis; the right lung was the most affected and, therefore, the approaches on this hemithorax were more common. The right vertical axilary thoracotomy (Bordonne technique) and wedge metastasectomy were the most used techniques. It was possible to observe by statistical methods and Kaplan Meier’s tables for event-free survival and global survival, a significant difference in connection with the distribution of times and a high morbidity and mortality, in spite of metastasectomy(AU)