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Jessica Donington

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    MS 23 - Management of N2 NSCLC: What “Operable” Means? (ID 545)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      MS 23.02 - When Do Surgeons Quit Resection During Surgery? (ID 7750)

      14:30 - 16:15  |  Presenting Author(s): Jessica Donington

      • Abstract
      • Presentation
      • Slides

      Reasons surgeons “quit” cancer operations are typically related to finding additional sites of disease, inability to perform necessary dissection, or disappearance of previously identified disease. In the setting of N2 positive non-small cell lung cancer (NSCLC) the disappearance of disease is not a consideration, so occult sites of disease or inability to perform safe hilar or mediastinal dissection are the most common reasons to back out of an operation once started. Incredibly precise pre-resection imaging has made this an uncommon scenario. Imaging techniques include functional and molecular correlates, and 3 and 4 dimensional reconstructions, which improve detection of very small lesions and appreciation of tumor interactions with adjacent structures. That being said, N2 involvement denotes locally advanced and often aggressive disease and use multimodality treatments and therefore the risk for unexpected findings in the operating room which alter resectability are more frequent than in early stage disease. Occult or unexpected disease encountered by thoracic surgeons in the operating room typically involves the parietal pleura, as occult carcinomatous pleuritis. Additional pulmonary nodules and unanticipated milliary spread are far less common. Pleural studding is defined as M1a disease in the 8[th] edition of AJCC staging. Chemotherapy is the recommended treatment for radiographically identified pleural involvement, but management recommendations are slightly less clear for disease found at the time of surgery. Pulmonary resections are generally contraindicated, but several investigators report favorable outcomes for those who can undergo macroscopic complete resection.[1,2] Carcinomatous pleuritis can escape radiographic detection, the incidence of occult disease at thoracotomy ranges from 1.5% to 4.5% for all lung cancer resections,[3] and is associated with large tumors, non-squamous histology, and lymph node involvement.[2] Carcinomatous pleuritis can escape radiographic detection, the incidence of occult disease at thoracotomy ranges from 1.5% to 4.5% for all lung cancer resections,[] and is associated with large tumors, non-squamous histology, and lymph node involvement. Intraoperative pleural lavage cytology (PLC) is a technique used for detecting subclinical dissemination of malignant cells in the pleural cavity. The boundary between malignant pleural effusion and positive PLC is not particularly well defined and most reports demonstrate a negative impact on prognosis in resected patients, but positive PLC does not upgrade tumors in the current TNM staging system. It also does not preclude resection in a patient with otherwise resectable disease. Similar to pleural studding positive cytology is consistently found to be more common in patients with higher stage and nodal involvement.[4] The presence of bulky N2 disease can greatly increase the complexity of hilar and mediastinal dissection. Modern techniques and intraoperative tools have increased surgeons ability to remove structures once considered unresectable including the spine, carina, and superior vena cava, but direct tumor extension or nodal involvement of the trachea, heart or great vessels can make safe resection impossible. Preoperative imaging typically allows for appropriate planning and decision making about these types of complex resections and controversy exists as to appropriateness of such resections in the setting of N2 disease. Induction therapy can make the pre-operative assessment of involved structures more complicated, differentiation between tumor and treatment effect is not always clear and therefore many surgeons make resection decisions on pre-treatment imaging. A more common scenario in thoracic oncology is that of the patient with marginal pulmonary reserve in whom the hilar resection is complicated by extensive nodal involvement or treatment effect; a pneumonectomy is technically feasible and would result in complete resection, but the patient would not tolerate that extensive a resection. Sleeve resections are used whenever possible, but widespread hilar and mediastinal scarring can sometimes exclude any safe surgery other than a pneumonectomy. The amount of fibrosis and scarring encountered at resection following induction therapy remains unpredictable. It is known to increase with time, which is why resection is recommended within 12 weeks induction therapy, but within that window, it can be quite variable. Review of recent large prospective trials for resectable IIIA NSCLC can help shed light on how frequently and why surgeons cannot complete the planned resection for N2 positive NSCLC. In the recent SAAK trial which compared induction chemotherapy to induction chemoradiotherapy in high volume operative centers in Europe, all patients who were taken to surgery, had a pulmonary resection, but R2 resections occurred in 3% of the trimodality group and 8% of the bimodality, reasons for incomplete resection were not delineated.[5] In the recent report of pooled data from RTOG 0229 and 0839, evaluating surgical outcomes after high dose induction chemo-radiotherapy, 7 of the 99 patients brought to surgery were not resected, 2 due to occult pleural metastasis, 2 because of persistent N2 involvement in patient with limited pulmonary reserve, and 3 were “unresectable”, 2 because complete resection would require a pneumonectomy and they had poor pulmonary reserve and one due to extensive mediastinal fibrosis.[6] These trials were all limited to experienced thoracic surgeons, indicating that the inability to complete a planned resection for IIIA NSCLC remains a rare but real phenomenon even in skilled surgical hands. References 1. Fukuse, T., et al., The prognostic significance of malignant pleural effusion at the time of thoracotomy in patients with non-small cell lung cancer. Lung Cancer, 2001. 34(1): p. 75-81. 2. Iida, T., et al., Surgical Intervention for Non-Small-Cell Lung Cancer Patients with Pleural Carcinomatosis: Results From the Japanese Lung Cancer Registry in 2004. J Thorac Oncol, 2015. 10(7): p. 1076-82. 3. Fukui, T. and K. Yokoi, The role of surgical intervention in lung cancer with carcinomatous pleuritis. J Thorac Dis, 2016. 8(Suppl 11): p. S901-S907. 4. Toufektzian, L., et al., Pleural lavage cytology: where do we stand? Lung Cancer, 2014. 83(1): p. 14-22. 5. Pless, M., et al., Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet, 2015. 386(9998): p. 1049-56. 6. Donington, J., et al. safety and Feasibility of Lobectomy folowing Concurrent Chemotherapy and High Dose Radiation for Stage IIIA NSCLC: Pooled Surgical Results of NRG Oncology RTOG 0229 and 0839. in American Asociation for Thoracic Surgery. 2017. Boston, MA.

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