Faculty Bibliography

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 miliary spread are far less common. Pleural studding is defined as M1a disease in the 8th 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

INTRODUCTION: Multimodality therapy has curative potential in locally advanced NSCLC. Mediastinal nodal sterilization (MNS) after induction chemoradiotherapy (CRT) can serve as an intermediate marker for efficacy. NRG Oncology Radiation Therapy Oncology Group (RTOG) 0229 demonstrated the feasibility and efficacy of combining full-dose radiation (61.2 Gy) with chemotherapy followed by resection and chemotherapy. On the basis of that experience and evidence that EGFR antibodies are radiosensitizing, we explored adding panitumumab to CRT followed by resection and consolidation chemotherapy in locally advanced NSCLC with a primary end point of MNS. METHODS: Patients with resectable locally advanced NSCLC were eligible if deemed suitable for trimodality therapy before treatment. Surgeons were required to demonstrate expertise after CRT and adhere to specific management guidelines. Concurrent CRT consisted of weekly carboplatin (area under the curve = 2.0), paclitaxel (50 mg/m2), and 60 Gy of radiation therapy delivered in 30 fractions. There was a 2:1 randomization in favor of panitumumab at 2.5 mg/kg weekly for 6 weeks. The mediastinum was pathologically reassessed before or at the time of resection. Consolidation chemotherapy was weekly carboplatin (area under the curve = 6) and paclitaxel, 200 mg/m2 every 21 days for two courses. The study was designed to detect an improvement in MNS from 52% to 72%. With use of a 0.15 one-sided type 1 error and 80% power, 97 patients were needed. RESULTS: The study was opened in November 2010 and closed in August 2015 by the Data Monitoring Committee after 71 patients had been accrued for futility and excessive toxicity in the experimental arm. A total of 60 patients were eligible: 19 patients (86%) who received CRT and 29 (76%) who received CRT plus panitumumab and underwent an operation. With regard to postoperative toxicity, there were three grade 4 adverse events (13.6%) and no grade 5 adverse events (0%) among those who received CRT versus six grade 4 (15.8%) and four grade 5 adverse events (10.5%) among those who received CRT plus panitumumab. The MNS rates were 68.2% (95% confidence interval: 45.1-86.1) and 50.0% (95% confidence interval: 33.4-66.6) for CRT and CRT plus panitumumab, respectively (p = 0.95). CONCLUSION: The addition of panitumumab to CRT did not improve MNS. There was an unexpectedly high mortality rate in the panitumumab arm, although the relationship to panitumumab is unclear. The control arm had outcomes similar to those in NRG Oncology RTOG 0229.

Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The IASLC and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for non-small cell lung cancer, small cell lung cancer, and mesothelioma. Quality and value of care and perspectives on the future of lung cancer research and treatment have also been included in this concise review.

PURPOSE: This guideline presents evidence-based recommendations for stereotactic body radiation therapy (SBRT) in challenging clinical scenarios in early-stage non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to perform a systematic literature review on 4 key questions addressing: (1) application of SBRT to operable patients; (2) appropriate use of SBRT in tumors that are centrally located, large, multifocal, or unbiopsied; (3) individual tailoring of SBRT in "high-risk" clinical scenarios; and (4) SBRT as salvage therapy after recurrence. Guideline recommendations were created using a predefined consensus-building methodology supported by American Society for Radiation Oncology-approved tools for grading evidence quality and recommendation strength. RESULTS: Although few randomized trials have been completed for SBRT, strong consensus recommendations based on extensive, consistent publications were generated for several questions, including recommendations for fractionation for central tumors and surgery versus SBRT in standard-risk medically operable patients with early-stage NSCLC. Lower quality evidence led to conditional recommendations on use of SBRT for tumors >5 cm, patients with prior pneumonectomy, T3 tumors with chest wall invasion, synchronous multiple primary lung cancer, and as a salvage therapy after prior radiation therapy. These areas of moderate- and low-quality evidence highlight the importance of clinical trial enrollment as well as the role of prospective data registries. CONCLUSIONS: SBRT has an important role to play in treating early-stage NSCLC, particularly for medically inoperable patients with limited other treatment options. Shared decision-making with patients should be performed in all cases to ensure the patient understands the risks related to SBRT, the side effects, and the alternative treatments available.

Cardiac surgery patients with infected implantable cardioverter defibrillator hardware face high morbidity with both surgical and nonoperative management options. We present a case of infected epicardial patch defibrillator leads in a patient with prohibitively high risk of death with open surgical removal. As a less morbid alternative, an Eloesser flap was used to convert his presenting mediastinal empyema necessitans into a chronic, manageable wound.

Marjolin's ulcers typically result from long-term chronic inflammation of a squamous surface, most often related to burns and other scars. This report describes a squamous cell carcinoma arising from the pleural surface in a patient with a chronically neglected Eloesser flap.