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K. Yokoi
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ES 05 - Surgical Skills (ID 514)
- Event: WCLC 2017
- Type: Educational Session
- Track: Surgery
- Presentations: 6
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ES 05.01 - Strategy for N2 NSCLC (ID 7599)
15:45 - 16:00 | Presenting Author(s): Joe B Putnam
- Abstract
- Presentation
Abstract:
The clinical stage is the clinician’s best and final estimate of the extent of the disease prior to the initiation of definitive therapy. As such, the clinical stage creates the foundation for all cancer treatment recommendations. Patients with lung cancer and metastasis to the ipsilateral mediastinal and/or subcarinal lymph node(s) (LN) have a nodal descriptor of N2. Such N2 metastasis reflects a biologically advanced disease with spread beyond the primary tumor in the lung itself. In the forthcoming eighth addition of the TNM classification for lung cancer, the current (7th edition) nodal descriptors and location for both clinical and pathological nodal status (N0 to N3) adequately predict prognosis. Although for lung cancer, nodal status is based on the anatomic location of the involved node, and not on the number of metastatic lymph nodes, future staging models could assess the number of involved nodes and location.(1) Determination of metastases to mediastinal lymph nodes constitutes a critical point in staging and treatment recommendations. Computed tomography and FDG-PET + CT scans are helpful to guide treatment decisions; invasive staging is still recommended to confirm mediastinal nodal involvement. (2) (3) (4) Invasive staging for diagnosis of N2 LN includes cervical mediastinoscopy (CME) or mediastinotomy (Chamberlain’s procedure), endoscopic bronchial ultrasound (EBUS), or esophageal ultrasound (EUS). The use of CME regardless of radiographic evidence of nodal involvement (“routine mediastinoscopy”) is not a cost effective approach, and adds little to the accuracy of staging in patients with an adequate noninvasive preoperative evaluation. (5) Endobronchial ultrasound combined with mediastinoscopy (2;4) can be effective. VATS techniques can evaluate enlarged level 5 or 6 lymph nodes, and as well, enlarged level 8 or 9 or low level 7 lymph nodes. Esophageal ultrasound (EUS) guided aspiration can be used for level 7 and AP window LN Patients with clinically early stage NSCLC (cStage I or II), who have complete resection (R0) and subsequently identified microscopic or occult N2 metastases, represent a biologically favorable subset with improved survival following adjuvant therapy. Surgery alone for cStage IIIA (N2) lung cancer is infrequently performed however, selected patients may benefit from a multidisciplinary approach to treatment which include local and systemic components. (6). Definitive concurrent chemoradiotherapy is commonly recommended for N2 disease given the identifiable locally advanced NSCLC and likely occult systemic metastases. . Induction chemoradiotherapy has been evaluated for treatment of clinical stage IIIA (N2) NSCLC. (7;8) In these two phase III trials, surgery did not provide an overall survival benefit; however, in an exploratory analysis, induction therapy followed by lobectomy had improved survival. Multidisciplinary team discussions for individual patients are essential to optimize benefits of treatment. In selected resectable IIIA NSCLC patients, induction chemoradiotherapy followed by resection is an alternative treatment to chemoradiotherapy alone. (6) The Society of Thoracic Surgery National General Thoracic Surgery Database evaluated identified only 3319 patient with cStage IIIA (N2) NSCLC who underwent resection between 2002 and 2012. (9) Patients were >65 years of age and only 46% were treated with induction therapy. 93% had FDG PET scans, and 51% were coded as having undergone invasive mediastinal staging. Nodal over-staging occurred in 43% of patients. Lobectomy was the most common procedure (69%). The unadjusted 5 year survival following induction therapy was 35%. Selection of patients for resection may depend on the number of ipsilateral LN stations involved, and the ability of induction therapy to create a clinical post-induction yN0 nodal status. Endobronchial ultrasound (EBUS) is used initially to diagnosis ipsilateral LN metastasis and exclude contralateral metastasis. Following induction therapy, repeat EBUS may confirm yN0 status of the previously involved LN, and be validated by cervical mediastinoscopy. The surgeon must answer this question for each patient with N2 disease: When does resection following induction therapy consistently provide better survival than definitive C+RT? Large pragmatic clinical trials may facilitate new knowledge in this area. Regardless of approach (open or minimally invasive techniques), a mediastinal lymph node dissection is recommended. A recent study utilizing the National Cancer Database from the American College of Surgeons Commission on Cancer, demonstrated that with Stage I NSCLC better survival was associated with resecting 10 or more lymph nodes to optimally confirm stage I status.(10) Although this is not a therapeutic intervention, it emphasizes the need for mediastinal lymph node dissection to ensure accuracy by decreasing variability in the mediastinal dissection, and optimizing the accuracy of the pathologic staging. Reference List (1) Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste JF, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revision of the N Descriptors in the Forthcoming 8th Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2015 Dec;10(12):1675-84. (2) Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013 May;143(5:Suppl):211S-50S. (3) Stamatis G. Staging of lung cancer: the role of noninvasive, minimally invasive and invasive techniques. European Respiratory Journal 2015 Aug;46(2):521-31. (4) Detterbeck FC, Postmus PE, Tanoue LT. The stage classification of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013 May;143(5:Suppl):191S-210S. (5) Fernandez FG, Kozower BD, Crabtree TD, Force SD, Lau C, Pickens A, et al. Utility of mediastinoscopy in clinical stage I lung cancers at risk for occult mediastinal nodal metastases. J Thorac Cardiovasc Surg 2015;149(1):35-41. (6) Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA, et al. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013 May;143(5:Suppl):314S-40S. (7) Albain KS, Swann RS, Rusch VW, Turrisi AT, III, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet 2009 Aug 1;374(9687):379-86. (8) van Meerbeeck JP, Kramer GW, Van Schil PE, Legrand C, Smit EF, Schramel F, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst 2007 Mar 21;99(6):442-50. (9) Boffa D, Fernandez FG, Kim S, Kosinski A, Onaitis MW, Cowper P, et al. Surgically Managed Clinical Stage IIIA-Clinical N2 Lung Cancer in The Society of Thoracic Surgeons Database. Ann Thorac Surg 2017 Aug;104(2):395-403. (10) Samayoa AX, Pezzi TA, Pezzi CM, Greer GE, Asai M, Kulkarni N, et al. Rationale for a Minimum Number of Lymph Nodes Removed with Non-Small Cell Lung Cancer Resection: Correlating the Number of Nodes Removed with Survival in 98,970 Patients. Annals of Surgical Oncology , 2016 23, Suppl 5:1005-1011.
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ES 05.02 - Superior Sulcus Tumor (ID 7600)
16:00 - 16:15 | Presenting Author(s): Valerie W Rusch
- Abstract
- Presentation
Abstract:
The unique location of Pancoast tumors makes complete resection challenging and usually includes the upper lobe, involved chest wall with or without the subclavian vessels, portions of the vertebral column and T1 nerve root, and dorsal sympathetic chain. Several approaches are used depending on tumor location. Posterior Approach The patient is positioned in the lateral decubitus position, rotated slightly anteriorly to expose the paravertebral region. The chest is explored via a posterolateral thoracotomy in the 5[th] intercostal space. If the tumor appears resectable, the incision is extended to the base of the neck posteriorly and around the anterior border of the scapula anteriorly. The scapula is elevated with an internal mammary retractor. The scalene muscles are detached from the first and second ribs. Involved ribs are divided anteriorly. Dissection is carried along the superior border of the first rib in the subperiosteal plane. The erector spinae muscles are retracted off the thoracic spine to expose the costovertebral gutter. The transverse processes and rib heads are resected en-bloc at the lateral border of the facet joint. The chest wall is retracted anteriorly, and the intercostal nerves ligated before division to prevent cerebrospinal fluid leak. Thoracic nerve roots below T1 are transected without neurologic sequelae. Since the T1 nerve root provides motor innervation to the hand, it is ligated only in cases of tumor invasion. Division of the C8 nerve root will result in permanent arm/hand paralysis. The detached chest wall is allowed to fall into the chest cavity and an upper lobectomy and lymph node dissection is completed. Reconstruction of the chest wall is necessary when the defect is larger than the first three ribs and can be performed with a 2 mm thick PTFE patch. Tumors Involving the Vertebral Bodies and Epidural Region Vertebral body invasion by Pancoast tumors no longer a contraindication to surgical resection because of contemporary spine instrumentation. With multimodality therapy, T4 lesions with vertebral body or epidural extension can be resected with curative intent. We use spine MRI to divide tumors into four classes, A-D, based on the degree of spinal column and neural tube involvement. Class A and B tumors are T3 lesions amenable to complete R0 resection. Class C and D tumors are T4 lesions not amenable to en-bloc resection but can still be completely resected. Class C tumors extend into the neural foramina with limited or no vertebral body involvement but have unilateral epidural compression. Class D tumors involve the vertebral column, either the vertebral body and/or lamina with or without epidural compression. Class A, B and some class C tumors are approached through a posterolateral thoracotomy. A high-speed drill is used to remove involved vertebral bodies. The posterior longitudinal ligament is removed and provides a margin on the anterior dura. The disc spaces adjacent to the tumor are exenterated in order to aid in spinal fixation. Anterior reconstruction alone is sufficient for resections of 1-2 vertebral bodies. Autologous bone from the iliac crest or non-diseased rib, allograft fibula, methymethacrylate with Steinman pins, or corpectomy cages can all be used for reconstruction. Patients requiring any degree of epidural decompression in the upper thoracic spine undergo combined posterior and anterior approach. Long segment posterolateral spinal instrumentation and fusion avoids the development of debilitating deformity. Class D tumors involving the posterior elements (spinous process, laminae, and pedicles) are also resected through a combined posterior/anterior approach. Patients are first positioned prone and a posterior midline incision made. The involved areas of the spinous process, laminae, and pedicles are resected. Epidural tumor is dissected off the dura and a multilevel resection of affected nerve roots done. Posterior fixation is accomplished in order to maintain coronal and sagittal stability. Muscle flap rotation by a plastic surgeon can be done to reduce the risk of skin breakdown and infection of the spine hardware. The incision is then closed, the patient turned to the lateral decubitus position, a posterolateral thoracotomy performed, and the lung and chest wall resection completed. Anterior Approaches Pancoast tumors involving the subclavian vessels are best approached anteriorly, using the anterior transcervical approach originally described by Dartevelle and modified by others. The patient is positioned supine with the neck hyperextended and the head turned to the opposite side of the lesion. An inverted L-shaped incision is carried down the anterior border of the sternocleidomastoid muscle and extended below the clavicle to the level of the second intercostal space, then turned horizontally following a parallel line below the clavicle to the deltopectoral groove. The sternal attachment of the sternocleidomastoid is divided along with the insertion of the pectoralis major. The scalene fat pad and lymph nodes are excised. If the tumor is resectable, the upper part of the manubrium is divided and the incision carried into the second intercostal space via an L-shaped incision. The involved section of the subclavian vein is resected but not reconstructed. The anterior scalene muscle is divided at its insertion onto the first rib. The phrenic nerve is preserved. The subclavian artery is resected and reconstructed with a 8 or 10 mm PTFE graft. The middle scalene muscle is detached from the first rib to expose the C8 and T1 nerve roots. The ipsilateral prevertebral muscles and paravertebral sympathetic chain and stellate ganglion are resected off the anterior aspect of the vertebral bodies of C7 and T1. TheT1 nerve root is commonly divided just lateral to the T1 intervertebral foramen. The anterolateral arch of the first rib is divided at the costochondral junction and the second rib is divided at its midpoint. The third rib is dissected on its superior border in a posterior direction toward the costovertebral angle and the first two through three ribs are disarticulated from the transverse processes. From this cavity, an upper lobectomy is completed. If exposure for the lobectomy and chest wall resection is inadequate, the anterior incision is closed, the patient turned into the lateral decubitus position and the rest of the resection performed via a posterolateral thoracotomy
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ES 05.03 - Management of Early Stage Lung Cancer (ID 7601)
16:15 - 16:30 | Presenting Author(s): Norihiko Ikeda | Author(s): T. Ohira, Naohiro Kajiwara
- Abstract
- Presentation
Abstract:
In recent years, the number of early stage lung cancers has enormously increased mainly due to frequent use of chest CT in routine practice or screening purpose. Both curability and non-inavasiveness are required especially for such early disease. Increased number of VATS lobectomy and sublobar resection for selected patients is the international trend in such situation. Diagnosis: Retrospective data revealed that the sensitivity of conventional bronchoscopic examination for peripheral cancer < 2cm is only 34%. The combination of Virtual bronchoscopic navigation and EBUS guide-sheath has demonstrated the improved sensitivity, thus this new combination strategy should be necessary for differential diagnosis of small cancers detected by chest CT[1)]. Surgical procedure: A total of 38000 lung cancers were resected in Japan in 2013 and 70% of surgeries were video-assisted[2)]. Segmentectomy has been performed intentionally mainly for lung cancer 2cm or less in diameter. Several comparative studies between lobectomy and segmentectomy for tumors < 2cm showed no significant difference in survival[3)]. Recently, segmentectomy is selected based on the size and high resolution CT (HRCT) findings of the tumor. The proportion of consolidation diameter to tumor diameter correlates with biological malignancy and the establishment of robust image criteria predicting non-invasive cancer is desirable to find candidates for segmentectomy. The Japan Clinical Oncology Group (JCOG) conducted a prospective study to recognize the relationship between HRCT finding and pathological non-invasiveness in clicical stage IA cancer (JCOG0201)[4)]. This study revealed that adenocarcinoma <2.0 cm with <0.25 consolidation to the maximum tumor diameter showed pathological non-invasiveness in 98.7% and this criterion could be used to predict early lung cancer preoperatively[5)]. Based on the result of JCOG0201, two prospective studies were performed and finished recruitment, phase II trial of wide wedge resection for radiological non-invasive adenocarcinoma (tumor diameter 2cm or less and consolidationratio<0.25) (JCOG0804) and randomised phase III trial for radiological invasive adenocarcinoma (tumor diameter 2cm or less and consolidation ratio>0.25) to evaluate non-inferiority in OS of segmentectomy compared to lobectomy (JCOG0802)[6)]. The indication of segmentectomy will be demonstrated by the results of these studies. Clinical research: PET-CT has been routinely used for clinical staging and the standardized uptake value (SUV) of the main tumor is recognized to be as a predictor of the clinicopathological characteristics and prognosis. Analyses of 610 resected stage IA adecocarcinoma showed that maxSUV and GGO ratio cutoffs to predict recurrence were 2.9 and 25%, respectively. They were also related to nodal metastasis, histological tumor invasiveness and recurrence. The 5-year RFS of cases with maxSUV <2.9 (n=456) was 95%, while cases with maxSUV>2.9 (n=154), 72% (p<0.001)[7)]. Our result showed that maxSUV cutoff of possibility for recurrence was 2.6 in adenocarcinoma, which was also related to nodal metastasis and histological tumor invasiveness. The 3-year relapse-free survival was 99%/78% (maxSUV lower/higher than 2.6) and following multivariate analysis, pathological nodal status and SUVmax were found to be independent predictive factors for relapse-free survival. Surgical management of early stage lung cancer should be selected based on the tumor size and consolidation ratio on HRCT. The results of RCTs will demonstrate the indication of sublobar resection in near future. Further analysis is encouraged for the evaluation of biological aggressiveness in each case[8)]. References Asano F, Shinagawa N, Ishida T, et al. Virtual bronchoscopic navigation combined with ultrathin bronchoscopy. A randomized clinical trial. Am J Respir Crit Care Med 2013; 188:327-333 Committee for Scientific Affairs The Japanese Association for Thoracic Surgery, Thoracic and cardiovascular surgery in Japan during 2013 : Annual report by the Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg.2015;63:670-701. Okada M, Koike T, Higashiyama M, et al. Radical sublobar resection for small-sized non-small cell lung cancer: a multicenter study. J Thorac Cardiovasc Surg. 2006; 132: 769-775 Suzuki K, Koike T, Asakawa T, et al.: A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol 2011;6:751-756 Asamura H, Hishida T, Suzuki K, et al. Radiographically determined noninvasive adenocarcinoma of the lung: Survival outcomes of Japan Clinical Oncology Group 0201 J Thorac Cardiovasc Surg 2013;146:24-30 Nakamura K, Saji H, Nakajima R, et.al. A Phase III Randomized Trial of Lobectomy Versus Limited Resection for Small-sized Peripheral Non-small Cell Lung Cancer (JCOG0802/WJOG4607L) Jpn J Clin Oncol 2010;40:271–274 Uehara H, Tsutani Y, Okumura S, et al. Prognostic Role of Positron Emission Tomographyand High-Resolution Computed Tomography in Clinical Stage IA Lung Adenocarcinoma Ann Thorac Surg 2013;96:1958–1965 Tsutani Y, Miyata Y, Nakayama H,et al.. Sublobar resection for lung adenocarcinoma meeting node-negative criteria on preoperative imaging. The Annals of thoracic surgery. 2014;97:1701-1707
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ES 05.04 - Minimally Invasive Surgery for Lung Cancer, including Robotics (ID 7602)
16:30 - 16:45 | Presenting Author(s): Giulia Veronesi
- Abstract
- Presentation
Abstract:
During the last two-three decades the surgical approach for the treatment of lung cancer had significantly changed. Compared to the traditional posterolateral thoracothomy the introduction and diffusion of a more conservative muscle sparing lateral thoracothomy has shown a first change to lesser trauma for patients, but only with the advent of mininvasive surgery we have witnessed the real change in terms of improving the quality of life and reducing perioperative pain (1). According to some review articles (2) not only perioperative outcome was improved with MIS compared to thoracotomy but also advantages in terms of oncological outcome have been reported even if it is possible that some selection bias could have played a role in the review results. Many studies have confirmed the benefits for the patients treated with MIS compared to open including reduced pain, complications, blood trasfusions and postoperative stay, and improved quality of life, ahestetic and functional results (3). Different technique have been described with different number of small incisions but all have in common that no rib spreading is performed and the dissection is done looking at the monitor. The most common videothoracoscopic techniques are: a. the Cophenaghen approach with an anterior incision of 4-6 cm in the IV intercostal space and 2 more trocars is characterised by an anterior to posterior approach to the mediastinum. This technique has been described by Heine Hansen and by Mc Kenna (4); b. the posterior approach of the Edinburgh school has been described by William Walker and reproduces the posterior approach to the hylum similar to that of the posterolateral thoracothomy (5). In this technique the utility incision is posterior, in the auscultatory triangle and usually two or three additional ports are used; c. the single port described by Gaetano Rocco and Diego Gonzales Riva with a single incision of 4-8 cm usually in the V intercostal space through which the tools and the camera are inserted (6). More recently new approaches has been described including the microlobectomy and the subxhifoid approach. Both techniques are aimed to reduce the pain of the intercostal nerve injury by avoiding the utility incision in the intercostal space. Despite all these advantages for the patients the manual vats has been embraced by a minority of thoracic surgeons and the diffusion has been very slow mainly due to technical difficulties, like the limited visual information, limited freedom of movement, unstable camera platform and poor ergonomics, and doubts on oncological radicality. To overcome videothoracoscopic technical limitations, the micromechanic and robotic sophisticated technology has been introduced with the robotic surgical systems. Natural movements of the surgeon’s hands are translated into precise instrument movements inside the patient with tremor filtration. Three dimensional view offers a visual magnification that compensate the absence of haptic feedback. The robotic surgical system is the result of a long process of development aimed at producing a natural extension of the surgeon’s eyes and hands via the intermediation of a computer. In this way, the ease of movement obtained with open surgery is summated with the advantages of the minimally invasive technique. Since 2002, when the first robotic system for surgery was introduced, robot-assisted thoracic surgery (RATS) has been adopted by an increasing number of centres around the world, and today is used in ~10% of lobectomies in the US (7, 8). Two different techniques have been described in robotic thoracic surgery, the complete portal robotic lobectomy or segmentectomy (CPRL or CPRS) maynly used by surgeons of North American, characterised by 3-4 arms technique, CO2 insufflation, posterior to anterior hilar dissection and a specimen extraction incision at the end of the procedure (9); and the Robotic Assisted Thoracoscopic Surgery (RATS), characterized by a 4-arms approach, a utility incision since the beginning, no routine CO2 insufflation and anterior to posterior hilar dissection (10). To date, no randomized trials have reported comparative data on RATS vs. VATS or thoracotomy for lung cancer. Retrospective analysis comparing RATS vs. thoracotomy have revealed advantages for the RATS approach, especially shorter hospital stays and a lower complication rate but when compared to VATS, RATS produces similar or only slightly better results, the two being minimally invasive techniques with no need for rib separation. A few studies have reported RATS to be safer than VATS, with less conversions for bleeding, less complications and lengths of stay; in others, it was associated with lower postoperative consumption of pain killers and quicker return of patients to normal activity. In addition, lymph-node upstaging has been shown to be higher with RATS than with VATS, with a similar rate as thoracotomy. The main disadvantage of RATS is the higher costs of instrumentation and surgical kits. Nevertheless, the future will probably see reductions in the costs of robotics and improvements in the instrumentation, integration with 3D imaging to improve virtual reality, and more patients benefitting from minimally invasive procedures for lung malignancies. References 1. Demmy TL, Curtis JJ. Minimally invasive lobectomy directed toward frail and high-risk patients a case-control study. Ann Thorac Surg 1999;68:194-200. 2. Whitson BA, et al. Thoracoscopic versus thoracotomy approaches to lobectomy: differential impairment of cellular immunity. Ann Thorac Surg 2008;86:1735-44. 3. Bendixen M, et al. Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial. Lancet Oncol. 2016;17:836-44. 4. Hansen HJ, et al. Video-assisted thoracoscopic surgery (VATS) lobectomy using a standardized anterior approach. Surg Endosc. 2011;25:1263-9. 5. Walker WS, et al. Thoracoscopic pulmonary lobectomy. Early operative experience and preliminary clinical results. J Thorac Cardiovasc Surg. 1993;106:1111-7. 6. Gonzalez-Rivas D, et al. Uniportal video-assisted thoracoscopic bronchovascular, tracheal and carinal sleeve resections†. Eur J Cardiothorac Surg 2016;49 Suppl 1:i6-16. 7. Park BJ, et al. Robotic assistance for video-assisted thoracic surgical lobectomy: technique and initial results. J Thorac Cardiovasc Surg 2006;131:54-9. 8. Cerfolio RJ, et al. Initial consecutive experience of completely portal robotic pulmonary resection with 4 arms. J Thorac Cardiovasc Surg 2011;142:740-6. 9. Dylewski MR, et al. Pulmonary resection using a total endoscopic robotic video-assisted approach. Semin Thorac Cardiovasc Surg 2011;23:36-42. 10. Veronesi G, et al. Four-arm robotic lobectomy for the treatment of early-stage lung cancer. J Thorac Cardiovasc Surg 2010;140:19-25.
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ES 05.05 - Lung Cancer Surgery for High Risk Patients (ID 7603)
16:45 - 17:00 | Presenting Author(s): Claudio Suarez Cruzat
- Abstract
- Presentation
Abstract:
High risk lung cancer patients represent a challenge in thoracic oncology, they are often related to heavy smoke habit with increased cardiovascular or respiratory diseases that prevents for getting optimal results in their lung cancer treatment. In the other hand it is widely accepted that lobectomy and lymphadenectomy is the standard treatment for younger patients with adequate cardiopulmonary function, specially in solid lung cancer patients (1). High risk patients with early stage lung cancer, often undergo sublobar resections, regardless of histology or tumor size, which increases the risk of local recurrence and may decrease long-term survival. However, a significant group of these patients have a good prognosis, either because their histology or tumor size are favorable, they present slow growing tumors or because they can undergo anatomical sublobar resections and a lymphadenectomy that provides an adequate disease control. In patients without respiratory or cardiovascular impairement it is accepted that sublobar resections have the same possibility of controlling the disease than lobectomy for ground glass opacity lesions, partially solid lesions (<50%) or with invasion area less than 5mm (2,3,4). The biggest problem appears in high-risk patients with solid lesions, in whom sublobar resections have not demonstrated the same oncological performance compared to lobectomy. This group will face the dilemma of decreasing operative morbimortality and the risk of postoperative respiratory disability versus decreased global and disease-free survival (5). Reports and our own expeience with the treatment of T1 and T2 patients with segmentectomies and wedge resections suggests that it is appropriate to try these patients with economical resections to improve the quality of life and survival in a group of patients whose survival curve does not depend only on cancer, but it is also important the competitive causes of mortality (ex. cardiovascular disease, pulmonary fibrosis, emphysema) (5). In our group, we evaluate cardiovascular risk with echocardiography and provocative test for myocardial ischemia, preferably exercise stress test. Respiratory risk is evaluated with spirometry, DLCO and cardiopulmonary exercise testing (peak VO2 and ventilatory equivalent VE/VCO2) (6,7). If ppoFEV1 <60%, ppoDLCO <60%, V02 <10-15ml/kg/min and/or CO2 equivalent >35, values that show that the patient is high-risk or inoperable, we incorporate the patient to an exercise training program. Our protocol considers 1-1.5 hours/day of training, with progressive load to improve muscular strength, cardiovascular and respiratory capacity, associated with full medical treatment (LABA/LAMA inhalers plus inhaled and eventually systemic corticosteroids). After completing the training period, the patient is reevaluated and the treatment plan is defined: 1.- If he leaves the high-risk group (VO2 >15ml/kg/min with VE/VCO2 <35), he will receive standard oncological surgery, according to tumor size and radiological/histological findings (TNM, GGO vs solid component, invasion). 2.- If the surgical contraindication persists (VO2 <10ml/kg/min with VE/VCO2 >35), we prefer non-surgical treatments (like SBRT). In our institution, less than 5% of patients that enter the training program remain inoperable. 3.- If the patient persists in the high or moderate-risk group (VO2 10-15ml/kg/min with VE/VCO2 <35), we prefer sublobar resections. In patients where the tumor is pure GGO or predominantly GGO (<50% solid) and measure less than 2 cms, we perform a VATS wide wedge resection plus hilar and mediastinal sampling. Frozen section must confirm that less than 50% is invasive or invasion area is smaller than 5mm. Margins should be larger than 1cm to persevere with wedge resection. If these requirements are not met: solid tumors larger than 10mm or mostly solid/GGO tumors, or GGO tumors greater than 2 cm with >25% solid, or has an invasive component larger than 5mm, we perform an anatomic segmental resection, by VATS or thoracotomy, associated with hilar and mediastinal lymphadenectomy (2,8,9,10). 4.- Even in larger tumors, we will attempt segmental resection in high-risk patients. We consider that although the risk of local recurrence is high, the lower morbidity and mortality rate of sublobar resections justifies this approach in high-risk patients. We believe that a sublobar resection with margins larger than 1 cm, grant better quality of life than a patient who becomes oxygen dependent, dies in the postoperative period or has not been resected due to the impossibility of lobectomy. In our institution, we have a prospective registry of morbidity that allows us to evaluate M&M rate and the relation with VO2 in patients with lobar and sublobar resections (5,9).(Fig1) Finally, in those patients with solid tumors and lymphovascular invasion, that are staged as clinically an pathological N0, the problem is that the intralobar lymph nodes are not completely accessible or evaluable. This implies that actually the N1 barrier is not adequately studied with sublobar resections, especially in those patients undergoing a training program and become candidates to wedge or even anatomical segmental resections as a treatment choise. This lack of information may be acceptable in AIS or MIA tumors, but constitute a greater risk in patients with solid or partially solid tumors, and even greater risk in those with lymphovascular invasion in the paraffin section. Should we consider these patients as potential N1 and add treatment to avoid the risk of relapse? There is no evidence to support this approach yet, but we feel it should be considered. References 1.- De Zoysa MK et al. Is limited pulmonary resection equivalent to lobectomy for surgical management of stage I non-small-cell lung cancer? Interactive CardioVascular and Thoracic Surgery 14(2012) 816-20 2.-Asamura H et al. Radiographically determined noninvasive adenocarcinoma of the lung: Survival outcomes of Japan Clinical Oncology Group 0201. J Thorac Cardiovasc Surg 2013;146:24-30 3.- Sakurai H, Asamura H. Sublobar resection for early stage lung cancer. Transl Lung Cancer Res 2014;3(3):164-172 4.- Suzuki K, Asamura H et al. “Early” peripheral lung cancer: prognostic significance of Ground Glass Opacity on thin-section computed tomographic scan. Ann thorac Surg 2002;74:1635-9 5.- Nakamura H et al. Comparison of the surgical outcomes of thoracoscopic lobectomy, segmentectomy, and wedge resection for clinical stage I non-small-cell lung cancer. 2011 Apr;59(3):137-41. 6.- Shafiek et al. Risk of postoperative complications in chronic obstructive lung disease patients considered fit for lung surgery: beyond oxygen consumption. Eur J Cardiothorac Surg 2016; doi:10/1093/ejcts/ezw104 7.- Salati M, Brunelli A. Risk stratification in lung resection. Curr Surg Rep. 2016; 4:37 8.- Hattori A et al. Prognostic impact of the findings on thin section computed tomography in patients with subcentimetric non small cell lung cancer. JTO 2017;12(6):954-962 9.- Valenzuela R et al. Long term survival of lung cancer in Chile. JTO2017;12(1):S745-S746 10.-Aokage K et al. Limited resection for early-stage non-small cell lung cancer as function-preserving radical surgery: a review. Jpn J Clin Oncol,2017,47(1):7-11 Figure 1 Fig 1: Survival in Resected NSCLC Lung Cancer by peak VO2, adjusted by TNM Patients with peak VO2 less than 15 ml/kg/min present a worse survival. Data obtained in a serie of 55 patients in the last preoperative evaluation, after training. Clinica Santa María, Santiago, Chile
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ES 05.06 - Salvage Surgery (ID 7604)
17:00 - 17:15 | Presenting Author(s): Hans Hoffmann
- Abstract
- Presentation
Abstract:
Salvage thoracic surgery has become an increasingly common indication in patients with lung cancer (1). In principle, three different indicative fields of salvage surgery in patients with lung cancer can be distinguished: a) the surgical resection of a persistent or recurring primary lung tumor after stereotactic radiotherapy, b) salvage lung resection after definitive chemoradiation therapy for Stage III non-small-cell lung cancer, or c) palliative surgery in cases with e. g. massive haemoptyses or bronchial obstruction with treatment-resistant retention pneumonia. Common to all indications is that they are always individual case decisions. The published series are all retrospective, comprise only a small number of patients and refer to a long period at a single institution. All studies show that these operations are often surgically challenging and demanding and require careful consideration of individual patient related factors. The presentation will provide an overview of the current literature, and will discuss own clinical experiences from selected cases. SBRT is an increasingly used modality in patients with stage I lung cancer. Whereas in the past SBRT was typically considered an alternative to surgery for patients unfit or at high risk for surgery, the modality is now being used more often also for healthier, potentially operable patients. In a recent study from MD Anderson Cancer Center, Antonoff and colleagues presented a retrospective analysis of the largest series of pulmonary resections after local SBRT failure reported to date, along with a cumulative review that incorporates all patients who have been previously reported. (2) They demonstrated that resection after local failure of SBRT in highly select individuals is feasible and safe, and has an overall acceptable morbidity and mortality, albeit higher than what is typically observed in nonirradiated patients. It is of note that in their series the majority (73%) of patients underwent lobectomy, and only 24% of patients underwent sublobar resections. In considering salvage resection, the authors recommend careful consideration of the patient’s performance status and the likely extent of required resection, to be discussed thoughtfully both with the patient and in a multidisciplinary tumor board setting. Local recurrence is observed in 20% - 35% of patients after definitive chemoradiation therapy for Stage III non-small-cell lung cancer. In selected cases salvage surgery may be considered. A recent study from Italy identified 35 cases that underwent salvage surgery after definitive chemoradiation therapy for locally advanced non–small cell lung cancer over a period of 10 years, representing 1.2% of all lung resections for lung cancer performed at their institution. (3) The authors showed acceptable postoperative survival (2- and 3-year OS was 39% and 33%, respectively) and complication rates (25.7% of both minor and major complications). Another recent study from the Netherlands reported on 15 patients that underwent salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiation therapy for locally advanced non-small cell lung cancer. The authors concluded that selected patients with locoregional recurrence or persistent tumor after high dose chemoradiation therapy, can undergo salvage surgery with acceptable morbidity and mortality, even when a pneumonectomy is required (4). Factors that might have contributed to their favourable results included adequate pre-operative staging, ability to obtain an R0 resection and a good performance status. Based on the favourable results, the authors emphasised that medically operable patients presenting with locoregional recurrence or persistent tumor after definitive chemoradiation therapy for NSCLC, should have all treatment options reviewed in an experienced multidisciplinary tumor board. In conclusion, salvage surgery after stereotactic radiotherapy or after definitive chemoradiation therapy for Stage III non-small-cell lung cancer has become a new challenge for thoracic surgeons. References: 1. Van Schil PE. Salvage surgery after stereotactic radiotherapy: a new challenge for thoracic surgeons. J Thorac Oncol; 2010. p. 1881-2. 2. Antonoff MB, Correa AM, Sepesi B, Nguyen QN, Walsh GL, Swisher SG, Vaporciyan AA, Mehran RJ, Hofstetter WL, and Rice DC. Salvage pulmonary resection after stereotactic body radiotherapy: A feasible and safe option for local failure in selected patients. J Thorac Cardiovasc Surg; 2017;154(2):689-699. 3. Casiraghi M, Maisonneuve P, Piperno G, Bellini R, Brambilla D, Petrella F, Marinis FD, and Spaggiari L. Salvage Surgery After Definitive Chemoradiotherapy for Non–small Cell Lung Cancer. Seminars in Thoracic and Cardiovascular Surgery. Elsevier BV; 2017;. 4. Dickhoff C, Dahele M, Paul MA, van de Ven PM, de Langen AJ, Senan S, Smit EF, and Hartemink KJ. Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy for locally advanced non-small cell lung cancer. Lung Cancer; 2016;94:108-13.
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P1.08 - Locally Advanced NSCLC (ID 694)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.08-002 - Blood Supply to the Tumor Do Not Predict the Effect of Induction Therapy in Patients with Locally Advanced Lung Cancer (ID 8065)
09:30 - 09:30 | Author(s): K. Yokoi
- Abstract
Background:
Induction therapy is a promising optional treatment for locally advanced lung cancer including superior sulcus tumors. However, predictors of the effect and pathologic complete responses have not been well-known. We hypothesized that those tumors invading neighboring structures would be more sensitive to induction therapy owing to the richer blood supply to them from involved organs. The purpose of this study was, therefore, to evaluate predictors for pathologic complete responses of induction therapy and whether the volume of blood supply to the tumor could predict the efficacy of induction therapy.
Method:
Patients who underwent induction therapy followed by surgery for locally advanced lung cancer were retrospectively reviewed. The volume of blood supply to the tumor was defined as the CT value (HU; Hounsfield Unit) calculated by subtraction of the non-enhanced value from the contrast-enhanced value (divided early phase and late phase) at the maximal dimension of the tumor on dynamic CT before induction therapy. The measured areas of the tumor were encircled by freehand with disengaging of bony structures. The efficacy of induction therapy was categorized to the pathologic complete response (pCR) and residual tumor (pRT) group.
Result:
From 2005, 50 patients were enrolled in this study. There were 43 males and 7 females, with a median age of 63 years old. The tumors consisted of 38 T3 lesions and 12 T4 lesions (40 chest wall, 7 mediastinum, and 3 vertebrae). Induction therapy included chemoradiotherapy in 39 patients, chemotherapy in 6, and radiotherapy in 5, and the dose of radiation was 40Gy in 33 patients, 45Gy in 1, 50Gy in 6, and 60Gy in 4, respectively. All patients except one underwent a complete resection, and the pathologic complete response was obtained in 15 (30%). The mean CT values of early and late phases in pCR groups were 14.1±12 HU and 30.6±14 HU, and those in pRT were 15.3±13 HU and 35.3±19 HU, respectively. By a logistic regression analysis, smaller size of the tumor (less than 42 mm) was the only trend of the predictor for pCR (p = 0.064), whereas maximum standardized uptake value on FDG-PET and CT values of early and late phases on contrast-enhanced CT had no correlations toward pathologic complete responses.
Conclusion:
The volume of blood supply to locally advanced lung cancers did not predict the effect of induction therapy, whereas smaller sized tumor tended to have a better effective response in this study.
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P1.17 - Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies (ID 703)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.17-004 - Extrapleural Pneumonectomy for Patients with Stage IVa Thymoma: Pathological Evaluation of Disseminated Pleural Nodules (ID 8445)
09:30 - 09:30 | Author(s): K. Yokoi
- Abstract
Background:
The optimal treatment method for thymoma with pleural dissemination remains controversial. We have performed a multimodality treatment including extrapleural pneumonectomy (EPP) for patients with stage IVa thymoma and pleural dissemination. There are few literatures investigating malignant behavior of disseminated nodules at the parietal and visceral pleura. Therefore, whether complete resection can be accomplished by EPP is not known.
Method:
Our treatment strategy for those patients was induction chemotherapy with cisplatin, doxorubicin, and methylprednisolone (CAMP therapy), followed by thymectomy combined with EPP. We pathologically investigated parietal and visceral pleural nodules obtained by EPP in 8 patients with thymoma and pleural dissemination.
Result:
The median age was 49 (31 to 60) years old. Seven patients had stage IVa disease and 1 had recurrent disease. Preoperative CAMP therapy was performed in 5 patients. Macroscopic complete resection was archived in all patients. Parietal pleural invasions by disseminated nodules were found in 6 patients, invasions to the diaphragm in 6 and visceral pleural invasions in 7. Invasions into the muscle layer of the diaphragm were discovered in 4 patients. Pathological complete resection (R0) was archived in all patients, and the 5-year recurrence free survival rate was 80.0%.
Conclusion:
EPP could be a successful complete resection and might be beneficial for patients with stage IVa thymoma and pleural dissemination. In those some patients, resection of the muscle layer of the diaphragm is needed to obtain R0.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-013 - Identification of Proteasomal Catalytic Subunit PSMA6 as a Therapeutic Target for Lung Cancer through a Pooled shRNA Screen (ID 8867)
09:30 - 09:30 | Author(s): K. Yokoi
- Abstract
Background:
Recent advances in high-throughput genetic analysis revealed that single lung cancer cells harbour a number of genetic and epigenetic changes. Nevertheless, findings from cancer epidemiology and the experimental models of the multi-step lung carcinogenic process, which were developed by our group and others, suggested that only a handful of changes are ‘drivers’ whereas others are only ‘passengers’. Thus, it is very important to identify those that truly contribute to the oncogenic properties of cancer cells by performing functional screening. To this end, we performed screening with a pooled shRNA library in search for genes that are critical for the survival and/or proliferation of lung cancer cells using a lung cancer cell line.
Method:
NCI-H460 cell line was used for semi-genome-wide dropout viability analysis using a pooled shRNA library that targeted 5,043 genes. Two Cdk4/hTERT-immortalised normal human bronchial epithelial cell lines, HBEC3 and HBEC4 were used as controls. Pathway analysis was done using NIH-DAVID. Microarray gene expression analysis was done using Illumina Human WG-6 v3.0 Expression BeadChip for 163 non-small cell lung cancer (NSCLC) cell lines and 59 normal control cell lines. DNA copy number analysis with array CGH was done for 108 NSCLC cell lines. Proteasome activity was measured using a 20S proteasome activity assay kit. 20 pairs of resected lung cancer and matched normal lung samples were used for immunohistochemistry of PSMA6. Cell growth was evaluated by WST-1 colorimetric proliferation assay. Cell cycle analysis was done using FACS for cells stained with propidium iodide.
Result:
shRNA screening targeting 5,043 genes in NCI-H460 identified 51 genes as candidates for therapeutic targets. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array CGH data showed that PSMA6, a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of PSMA6 in lung cancer. Silencing of PSMA6 induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalised normal lung cell line.
Conclusion:
Our data suggested that PSMA6 serves as an attractive target with a high therapeutic index for lung cancer.
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P3.09 - Mesothelioma (ID 725)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.09-006 - Preoperative Six-Minute Walk Distance and Desaturation in Patients with Malignant Pleural Mesothelioma (ID 8762)
09:30 - 09:30 | Author(s): K. Yokoi
- Abstract
Background:
Surgery for malignant pleural mesothelioma (MPM) is an invasive procedure associated with high morbidity. MPM often invades adjacent structures such as the chest wall, diaphragm, and mediastinum. Therefore, pulmonary functions and levels of physical fitness are reduced in advanced MPM. The aim of this study was to characterize preoperative exercise capacity and relate it to pulmonary functions, oxygenation, and postoperative outcomes in patients with MPM.
Method:
A retrospective study was conducted on 18 patients with MPM who were scheduled to undergo extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) followed by postoperative rehabilitation at Nagoya University Hospital from July 2012 to April 2016 (Institutional Review Board approval No. 2015-0413). To estimate preoperative exercise capacity, 6-min walk test (6MWT) and oxygen saturation of a peripheral artery (SpO~2~) during the 6MWT were assessed. Grades III and IV of the Clavien-Dindo classification were defined as major postoperative complications.
Result:
The age was 65.8 ± 6.4 years. Preoperative 6-min walk distance (6MWD) was 465.9±96.7 m. Minimum SpO~2~ ranged from 86% to 97%. The 6MWD significantly correlated with inspiratory capacity (r=0.507, P<0.05) and % of predicted value of diffusing capacity of the lung for carbon monoxide (%DL~CO~) (r=0.470, P<0.05). The minimum SpO~2~ during 6MWT significantly correlated with % of predicted values of vital capacity (r=0.619, P<0.01) and total lung capacity (r=0.493, P<0.05) and postoperative days of extubation (r=-0.495, P<0.05). The preoperative partial pressure of oxygen in arterial blood significantly correlated with %DL~CO~ (r=0.505, P<0.05). There was a total of 13 major postoperative complications (8 respiratory failure, 2 pneumonia, 1 empyema, 1 atrial fibrillation, and 1 prolonged air leak) in 6 patients. There was no in-hospital death or death within 30 days after surgery. The incidence of major complications was significantly associated with longer stays in intensive care unit (3.3±1.8 vs. 1.7±1.0 days, P<0.05) and hospital (54.2±31.2 vs. 12.3±3.2 days, P<0.05) but not with preoperative physical status or pulmonary functions. Stays in hospital after EPP (n=7) were significantly longer than those after P/D (n=11) (median 28 vs. 12 days, P=0.01) but there was no significant difference in incidence of major complications between the EPP and P/D groups.
Conclusion:
Our results indicate that the 6MWT is a convenient and useful field test to assess preoperative physical status in patients with MPM. Future studies with a larger cohort are required to elucidate risk factors for postoperative morbidity and mortality.
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P3.16 - Surgery (ID 732)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Surgery
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.16-010 - Preoperative Six-Minute Walk Distance Is Associated with Complications of Pneumonia after Lung Resection (ID 8147)
09:30 - 09:30 | Author(s): K. Yokoi
- Abstract
Background:
Postoperative pulmonary complications such as pneumonia are significant negative predictors of short- and long-term survival after thoracic surgery. A preoperative cardio-pulmonary function is known as a predictor for postoperative pulmonary complications in patients with lung cancer. However, little is known about the relationship between preoperative exercise capacity and complication of pneumonia after lung resection. The 6-min walk distance (6MWD) measured by the 6-min walk test (6MWT) is a simple, safe, and inexpensive field test that can be used to evaluate the functional exercise capacity. We examined the association between preoperative 6MWD and development of postoperative pneumonia.
Method:
A retrospective study was conducted on patients with malignant lung tumors who were scheduled to undergo lung resection at Nagoya University Hospital from January 2014 to December 2015 (Institutional Review Board approval No. 2015-0413). Preoperative pulmonary function tests and 6MWT were assessed. A logistic regression model and receiver operating characteristic (ROC) curves were used to analyze clinical variables and compare the performance on 6MWD and percentages of predicted values of forced expiratory volume in 1 s (%FEV~1~) and diffusion capacity of the lung for carbon monoxide (%DLco).
Result:
The data from a total 321 patients including 283 with primary lung cancer and 38 with metastatic lung tumors were analyzed. Preoperative 6MWD significantly correlated with age, FEV~1~, forced vital capacity (FVC), %DLco, and serum albumin level. Pneumonia developed in 13 patients (4.0%) and the 6MWD of patients with pneumonia was significantly lower than that of patients without (413.9±89.0 vs. 495.2±93.2 m, p=0.002). Incidences of smoking history and comorbidity of COPD and interstitial lung disease were significantly higher and %FEV~1~, FEV~1~/FVC, %DLco, and serum albumin level were significantly lower in patients with pneumonia than in those without. Length of hospital stay after surgery was significantly longer in patients with pneumonia than in those without (30.4±29.6 vs. 7.4±7.0 days, p<0.001). In ROC analysis, 6MWD ≤450 m was a threshold for predicting postoperative pneumonia with 69.2% sensitivity and 71.1% specificity. A 6MWD ≤450 m, %FEV~1~ <80%, %DLco <80%, serum albumin <3.5 g/dL, and blood loss during surgery >200 g were significantly associated with development of postoperative pneumonia in a logistic model adjusted by age, sex, and primary lung cancer.
Conclusion:
Preoperative 6MWD is associated with development of pneumonia after lung resection for malignancies. Preoperative 6MWT is a useful screening tool in patients with primary and metastatic lung tumors.
