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Thomas D'Amico



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    GR 03 - Treatment Options for Early Stage Lung Cancer Patients with Limited Pulmonary Reserve (ID 522)

    • Event: WCLC 2017
    • Type: Grand Rounds
    • Track: Early Stage NSCLC
    • Presentations: 1
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      GR 03.03 - Minimally Invasive Surgery for Early Stage NSCLC (ID 7636)

      11:00 - 12:30  |  Presenting Author(s): Thomas D'Amico

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lobectomy with mediastinal lymph node dissection has been established as the most effective therapy for patients with resectable non-small cell lung cancer (NSCLC). Over the past 20 years, it has also been demonstrated that thoracoscopic (VATS) approaches are associated with better outcomes than open approaches. With the adoption of lung cancer screening protocols, more patients with early stage lung cancers (<2 cm) are going to be candidates for surgical resection, and some of these patients may benefit from anatomic sublobar resection (segmentectomy). The VATS approach to segmentectomy for stage I NSCLC has been shown to be feasible and safe and has found to be associated with decreased perioperative mortality and equivalent or improved overall survival when compared to segmentectomy via thoracotomy [1]. In addition, thoracoscopic segmentectomy may be particularly advantageous in patients with poor pulmonary function, with advantages in overall complication rates and other outcomes compared to open approaches. [2-6] Sublobar resection, as opposed to lobectomy, is appropriate for some patients with lung cancer: patients with ground glass opacities which are found to be adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or minimally invasive adenocarcinoma (MIA). In addition, sublobar resection is considered an acceptable compromise procedure for patient with tumors less than 2 cm in diameter and co-morbidities that preclude lobectomy, although lobectomy is associated with superior outcomes in most patients [7-8]. Specific indications to consider anatomic sublobar resection in patients with tumors <2cm include: age >80, compromised pulmonary function (FEV1 or DLCO <30% predicted), and favorable tumor location. [1, 2, 5, 7, 8] While it is feasible to achieve sublobar resection of any of the 10 segments, some of the segments are more technically challenging to remove. The typical (commonly performed) sublobar resections include superior segmentectomy (S6), lingulectomy (L S4+5), lingula-sparing left upper trisegmentectomy (L S1-3), posterior segmentectomy of the right upper lobe (R S2), and basilar segmentectomy (S 7-10). [9]. Outcomes Much of the data comparing outcomes of segmentectomy to lobectomy has come from patients with GGOs. When comparing patients with solid nodules <2cm, lobectomy is associated with better outcomes in several studies. In one study of 39,403 patients from the National Cancer Database (NCDB), 29,736 (74%) underwent lobectomy. [7] Of the 26% sublobar resections, 85% were wedge resections. In addition, lymph node evaluation not performed in 29%. Sublobar resection associated with smaller T and low-volume institutions. 5-year survival for lobectomy was superior to sublobar resection: 66% vs. 51% (P < 0.001). Another study analyzed the outcomes of patients with stage I lung cancer over 80 years of age, also from the NCDB. [8] In this study, sublobar resection was associated with significant reductions in survival, even among patients with T1a tumors and patients >85 years. Sublobar resection was inferior in all patients except those >85 years of age and Charlson/Deyo comorbidity index >2. It has been demonstrated that superior oncologic outcomes are associated with lobectomy; however, anatomic sublobar resection or non-anatomic (wedge) resection may be appropriate in selected patients. One study of the Society of Thoracic Surgeons database compared the morbidity and mortality of wedge resections (n=3733) with that of anatomic lung resections (lobectomy and segmentectomy) (n=3733) for stage I and stage II NSCLC using propensity-matched analysis. [10] The operative mortality rate was 1.2% for wedge resections versus 1.9% for anatomic resection (p=0.01) while major morbidity occurred in 4.5% for wedge resections and 9.0% for anatomic resection (p<0.01). The authors noted the mortality benefit was most apparent in patients with FEV1 less than 80% predicted although the morbidity benefit was observed regardless of age, lung function or type of incision. [10] Another study from the NCDB reported by Rosen and colleagues found a higher perioperative mortality rate of 4.2% for wedge resections for NSCLC. [11] In comparison, the segmentectomy and lobectomy groups had a perioperative mortality rate of 3.6% and 2.6%, respectively. The difference in perioperative rates may be explained by a difference in baseline comorbidities between the groups; the wedge resection group was sicker than the other two groups. Summary Thoracoscopic segmentectomy is a sound option for lung-sparing, anatomic pulmonary resection in selected patients for experienced thoracoscopic surgeons and can be safely applied to the treatment of a variety of pulmonary disorders, including small primary lung cancers, metastatic pulmonary disease, and benign disorders. The minimally invasive approach appears to have distinct advantages compared with thoracotomy, including reduced hospital length of stay, less postoperative pain, and fewer overall complications. The decision to perform sublobar anatomic resection for NSCLC may be complex, and the best candidates appear to be those with clinical stage I disease and tumors <2cm in diameter and other significant co-morbidities precluding lobectomy, or in patients with AAH, AIS, or MIA. References 1. Yang CF, and D'Amico TA. Open, thoracoscopic and robotic segmentectomy for lung cancer. Annals of cardiothoracic surgery. 2014;3:142-52. 2. Atkins BZ, Harpole DH, Jr., Mangum JH, Toloza EM, D'Amico TA, and Burfeind WR, Jr. Pulmonary segmentectomy by thoracotomy or thoracoscopy: reduced hospital length of stay with a minimally-invasive approach. The Annals of thoracic surgery. 2007;84:1107-12 3. Gulack BC, Yang C-F, Yerokun B, Tong BC, et al. A risk score to assist selecting lobectomy versus sublobar resection for non-small cell lung cancer. Ann Thorac Surg 2016; 102: 1814-20 4. Smith CB, Kale M, Mhango G, Neugut AI, Hershman DL, Mandeli JP, and Wisnivesky JP. Comparative outcomes of elderly stage I lung cancer patients treated with segmentectomy via video-assisted thoracoscopic surgery versus open resection. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9:383-9 5. Yang CF, and D'Amico TA. Thoracoscopic segmentectomy for lung cancer. The Annals of thoracic surgery. 2012;94(2):668-81 6. Zhong C, Fang W, Mao T, Yao F, Chen W, and Hu D. Comparison of thoracoscopic segmentectomy and thoracoscopic lobectomy for small-sized stage IA lung cancer. The Annals of thoracic surgery. 2012;94(2):362-7 7. Speicher PJ, Gu L, Gulack BC, Wang X, D'Amico TA, Hartwig MG, Berry MF. Sublobar resection for clinical stage IA non-small cell lung cancer in the United States. Clin Lung Cancer. 2016; 17: 47-55 8. Gulack BC, Yang CF, Speicher PJ, Kara HV, et al. Performing sublobar resection instead of lobectomy compromises the survival of stage I non-small cell lung cancer patients 80 years of age and older. (Under review) 9. Yerokun BA , Yang C-F, Gulack BC, Xuechan XL, Mulvihill MS, et al. A national analysis of wedge resection versus stereotactic body radiation therapy for clinical Stage IA non-small cell lung cancer. J Thorac Cardiovasc Surg 2017 Aug;154(2):675-686. Pham D, Balderson, S., and D’Amico, T.A. Technique of Thoracoscopic Segmentectomy. Operative Techniques in Thoracic and Cardiovascular Surgery. 2008;13: 188-203​. 10. Linden PA, D'Amico TA, Perry Y, Saha-Chaudhuri P, Sheng S, Kim S, and Onaitis M. Quantifying the safety benefits of wedge resection: a society of thoracic surgery database propensity-matched analysis. Ann Thorac Surg. 2014;98(5):1705-11; discussion 11-2. 11. Rosen JE, Hancock JG, Kim AW, Detterbeck FC, and Boffa DJ. Predictors of mortality after surgical management of lung cancer in the National Cancer Database. Ann Thorac Surg. 2014;98(6):1953-60.

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    MA 19 - Mesothelioma: Bench to Bedside (ID 680)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Mesothelioma
    • Presentations: 1
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      MA 19.09 - The Role of Neoadjuvant Chemotherapy in Patients with Malignant Pleural Mesothelioma (ID 10187)

      11:00 - 12:30  |  Author(s): Thomas D'Amico

      • Abstract
      • Presentation
      • Slides

      Background:
      The treatment of localized malignant pleural mesothelioma (MPM) involves multimodality therapy, however, there is no standard of care with respect to operative procedure and timing of chemotherapy. We analyzed data from a single institution to identify whether the use of pemetrexed-platinum neoadjuvant chemotherapy impacts survival.

      Method:
      Patients with histologically-proven MPM who had surgery from 1996 to 2016 were identified. Follow-up was complete for a median of 24 months. Survival was calculated from time of diagnosis to last follow up or death. Univariate and multivariate Cox proportional hazards were used.

      Result:
      From 1996 to 2016 we identified 376 patients. Mean age was 66+/-8 years and 54 (14%) were female. There was no difference in survival for pleurectomy/decortication or extrapleural pneumonectomy. Neoadjuvant chemotherapy significantly improved survival compared to surgery followed by chemotherapy (table 1). Multivariate analysis was significantly associated for increased survival for epithelioid histology, T-status, node positivity, and neoadjuvant chemotherapy (table 2).

      Table 1. Univariate Analysis
      Variable (n) Median survival (mo.) P value
      Gender Male (322) Female (54) 13.6 17.2 P=0.043
      Histology Epithelial (252) Mixed (91) Sarcomatoid (26) 18.3 12.1 6.5 P<0.0001
      T stage T 1-2 (33) T 3-4 (343) 42.6 14.3 P=0.0002
      N status N 0 (129) N 1-2 (113) 23.1 11.3 P<0.0001
      Neoadjuvant chemotherapy Yes (153) No (223) 19.8 11.3 P<0.0001
      Table 2. Cox Proportional Hazards Model
      Covariate Hazard Ratio 95% CI p-value
      Histology (ref: Epithelioid) Biphasic Sarcomatoid ref 1.66 4.24 [ref] [1.17-2.36] [1.77-10.1] ref 0.005 0.001
      T-status 3-4 vs 1-2 3.07 [1.32-7.15] 0.009
      Node-positivity 1.93 [1.40-2.66] <0.001
      Neoadjuvant chemotherapy 0.65 [0.47-0.91] 0.011
      Cox proportional hazards model including histology, t-status, n-status, and neoadjuvant chemotherapy C-index: 0.69

      Conclusion:
      Our results suggest that neoadjuvant chemotherapy increases survival and likely enhances the complete resection rate. These data are being evaluated in a multi-institutional cohort of five major mesothelioma programs in North America to improve guidelines for mesothelioma therapy.

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