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J. Mitchell
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GR 01 - Management of Challenging Clinical Scenarios in Localized Lung Cancer (ID 14)
- Event: WCLC 2015
- Type: Grand Rounds
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 4
- Moderators:G. Darling, J. Mitchell
- Coordinates: 9/08/2015, 14:15 - 15:45, 601+603
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GR01.01 - T4 NSCLC Involving the Great Vessels: Role for resection? (ID 1828)
14:15 - 15:45 | Author(s): D. Harpole
- Abstract
- Presentation
Abstract:
Usually NSCLC tumors that have invaded the central/mediastinal vascular structures are considered unresectable, and staged as T4 locally-advanced NSCLC and are treated with concurrent platinum-based chemotherapy and thoracic radiation with curative intent (60+Gy). However, subsets of good functional status patients with limited involvement (clinically node-negative; T4N0) have been selectively treated with surgical resection before or after additional therapy. This has been most commonly employed for tumor invasion at the base of one of the pulmonary veins with extension into the proximal left atrium or for right upper lobe tumors with segmental involvement of the superior vena cava. Smaller series exist for resection of lung tumors having primary extension into the cardiac chambers and aortic arch. There are no prospective trials, only manuscripts that detail decades-long retrospective single institution series. This presentation will review the literature and surgical approaches to NSCLC involving the great vessel with and without circulatory support. Surgical management of lung cancer invading the aorta or the superior vena cava. Misthos P, Papagiannakis G, Kokotsakis J, Lazopoulos G, Skouteli E, Lioulias A. Lung Cancer. 2007 May;56(2):223-7. Epub 2007 Jan 16. Extended resection of the left atrium, great vessels, or both for lung cancer. Tsuchiya R, Asamura H, Kondo H, Goya T, Naruke T. Ann Thorac Surg. 1994;57(4):960-5 Results of superior vena cava resection for lung cancer. Analysis of prognostic factors. Spaggiari L, Magdeleinat P, Kondo H, Thomas P, Leon ME, Rollet G, Regnard JF, Tsuchiya R, Pastorino U. Lung Cancer. 2004 Jun;44(3):339-46. 15 years single center experience with surgical resection of the superior vena cava for non-small cell lung cancer. Shargall Y, de Perrot M, Keshavjee S, Darling G, Ginsberg R, Johnston M, Pierre A, Waddell TK. Lung Cancer. 2004:357-63 Superior vena cava resection for lung and mediastinal malignancies: a single-center experience with 70 cases. Spaggiari L, Leo F, Veronesi G, Solli P, Galetta D, Tatani B, Petrella F, Radice D. Ann Thorac Surg. 2007 Jan;83(1):223-9; discussion 229-30 Left atrial resection for T4 lung cancer without cardiopulmonary bypass: technical aspects and outcomes. Galvaing G, Tardy MM, Cassagnes L, Da Costa V, Chadeyras JB, Naamee A, Bailly P, Filaire E, Pereira B, Filaire M. Ann Thorac Surg. 2014 May;97(5):1708-13 Results of primary surgery with T4 non-small cell lung cancer during a 25-year period in a single center: the benefit is worth the risk. Yildizeli B, Dartevelle PG, Fadel E, Mussot S, Chapelier A. Ann Thorac Surg. 2008 Oct;86(4):1065-75; Twelve-year experience with left atrial resection in the treatment of non-small cell lung cancer. Ratto GB, Costa R, Vassallo G, Alloisio A, Maineri P, Bruzzi P. Ann Thorac Surg. 2004 Jul;78(1):234-7. Review. Survival after extended resection for mediastinal advanced lung cancer: lessons learned on 167 consecutive cases. Spaggiari L, Tessitore A, Casiraghi M, Guarize J, Solli P, Borri A, Gasparri R Petrella F, Maisonneuve P, Galetta D. Ann Thorac Surg. 2013;95(5):1717-25 Superior vena caval resection in lung cancer. Lee DS, Flores RM. Thorac Surg Clin. 2014 Nov;24(4):441-7
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GR01.02 - Should All Lung Tumors Invading the Chest Wall Be Treated Like Pancoast Tumors? (ID 1829)
14:15 - 15:45 | Author(s): B. Stiles
- Abstract
- Presentation
Abstract:
Chest wall involvement is rare in patients with non-small cell lung cancer (NSCLC), occurring in <8% of patients (1). Invasion of the chest wall accords a T3 designation in both the 7[th] and in the newly proposed 8[th] edition TNM staging systems (2). The overall five-year survival for patients with clinically staged T3N0 NSCLC is approximately 45% (2). With clinically suspected nodal disease, even limited to N1 stations, survival is markedly worse. While cT3N2 NSCLC patients are designated stage IIIA and typically given neoadjuvant therapy, optimal treatment protocols are less clear for cT3N0 or even for cT3N1 patients with chest wall tumors, despite the fact that cT3N1 patients are also classified stage IIIA. An en bloc surgical resection of the involved lung and of the chest wall with or without adjuvant therapy has historically been the treatment algorithm of choice for these patients. Little data exists to determine whether neoadjuvant chemotherapy or chemoradiation might be beneficial in this setting. In contrast, the preferred treatment algorithm for a unique subset of chest wall tumors, Pancoast tumors, has been clearly defined (1). These T3 or T4 superior sulcus tumors arise in the apex of the lung and invade the chest wall at the level of the first rib or above, often with involvement of the brachial plexus, subclavian vessels, or spine. For these patients with clinical T3-4N0-1 disease, two carefully conducted prospective, multi-institutional trials demonstrated that induction chemoradiation therapy was associated with high rates of pathological response, improved resectability, and increased survival over historical controls (3,4). In the Southwest Oncology Group Trial 9416 (Intergroup Trial 0160), following neoadjuvant cisplatin and etoposide with concurrent radiation (45 Gy), 61% of patients had either a pathologic complete response or minimal microscopic residual tumor (3). Among all patients undergoing surgery, 94% were able to undergo an R0 resection. Patients with pathologic complete response had a marked advantage in five year overall survival (median survival not reached for complete responders versus 30 months for those with residual disease). Overall survival of the entire cohort was 44%, but was 54% after complete resection. Similar results were found in a multi-institutional trial from Japan (JCOG 9806), in which 21% of patients experienced a complete pathologic response following neoadjuvant therapy with mitomycin, vindesine, and cisplatin and concurrent radiation of 45 Gy (4). Among surgical patients, 89% underwent an R0 resection. Overall five-year survival for the cohort exceeded 50%, with survival of complete responders again especially favorable. The successful adoption of neoadjuvant therapy followed by surgery for Pancoast tumors raised the question of whether a similar induction strategy should be used in patients with other T3 chest wall tumors outside of the superior sulcus. Previous reports have suggested that prognostic factors for survival in patients with chest wall tumors include lymph node status and depth of chest wall invasion, but also completeness of surgical resection and completion of chemotherapy (5,6). It seems logical that neoadjuvant chemotherapy or chemoradiation may facilitate an R0 resection and that such therapy may be better tolerated preoperatively in patients undergoing potentially morbid chest wall resections. Along those lines, a prospective phase II study of trimodality therapy was performed in Japan (CJLSG 0801) for patients with T3N0 or T3N1 NSCLC involving the chest wall (7). Fifty-one patients were entered into the study, among whom 49 (96%) completed neoadjuvant cisplatin and vinorelbine with concurrent radiation (40 Gy) and among whom 44 (92%) underwent complete resection. Similar to prospective studies in NSCLC patients with superior sulcus tumors, in resected tumors there was a high rate of complete pathological response (25%) and of only minimal residual disease (65%). Treatment was relatively safe. However, one patient did die during neoadjuvant therapy secondary to infection following neutropenia and seven additional patients (16%) experienced grade 4 toxicity. Despite this, 86% of patients completed the induction regimen. Among the 29 patients (66%) who went on to surgery, 5 patients experiencing major complications and there was 1 postoperative mortality. Although median follow up was only 16 months, the 2-year overall and progression-free survival rates were excellent at 85% and 71% respectively. While the results of CJLSG 0801 perhaps make a compelling argument to treat chest wall tumors with neoadjuvant therapy prior to resection, several caveats must be considered. From previous studies, it would seem that nodal disease is the strongest indicator of the need for systemic therapy. However, previously reported rates of nodal disease for chest wall tumors are generally only between 20-40% (5). The rate of nodal disease reported in a recently published review of a Japanese registry of chest wall tumors was only 27% (8). These patients without nodal disease will not clearly benefit from systemic therapy. Furthermore, as opposed to Pancoast tumors, the rate of complete resection of chest wall tumors outside the superior sulcus is high even without neoadjuvant therapy, 88% in the Japanese registry study (8). This ability to obtain an R0 resection calls into question the need to include radiation therapy in the preoperative treatment regimen for most cT3N0 patients, given the potential added morbidity. In conclusion, it would seem most reasonable to utilize neoadjuvant therapy in chest wall tumors with clinical N1 nodal disease. These patients are designated as stage IIIA and need chemotherapy as part of their treatment regimen. Neoadjuvant therapy prior to surgery makes sense, although care should be taken to avoid complications that may prevent surgical resection. For T3N0 patients, the treatment algorithm is less clear. Conceptually, large bulky tumors in which it is expected that difficulty in obtaining negative margins surgically would seem to be good candidates for chemotherapy and radiation preoperatively. Further studies need to explicitly compare neoadjuvant versus adjuvant chemotherapy for T3N0 chest wall tumors and need to better evaluate whether there is any beneficial role of radiation in this challenging group of NSCLC patients. 1. Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in non-small cell lung cancer, diagnosis and management of lung cancer 3[rd] ed: American College of of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143(5):e3696S-e399S. 2. Rami-Porta R, Bolejack V, Crowley J et al. Proposals for the Revisions of the T descriptors in the forthcoming eight edition of the TNM classification for lung cancer. J Thorac Oncol 2015;10:990-1003. 3. Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Clin Oncol 2007;25:313-318. 4. Kunitoh H, Kato H, Tsuboi M, et al. Phase II trial of preoperative chemoradiotherapy followed by surgical resection in patients with superior sulcus non-small-cell lung cancers: report of Japan Clinical Oncology Group Trial 9806. J Clin Oncol 2008;26:644-649. 5. Riquet M, Arame A, Le Pimpec Barthes F. Non-small cell lung cancer invading the chest wall. Thorac Surg Clin 2010;20:519-527. 6. Lee CY, Syun CS, Lee JG, et al. The prognostic factors of resected non-small cell lung cancer with chest wall invasion. World J Surg Onc 2012;10:9. 7. Kawaguchi K, Yokoi K, Niwa H, et al. Trimodality therapy for lung cancer with chest wall invasion: initial results of a phase II study. Ann Thorac Surg 2014;98:1184-91. 8. Kawaguchi K, Miyaoka E, Asamura H, et al. Modern surgical results of lung cancer involving neighboring structures: a retrospective analysis of 531 pT3 cases in a Japanese Lung Cancer Resistry Study. J Thorac Cardiovasc Surg 2012;144:431-7.
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GR01.03 - T4 Lung Tumors According to the New Classification - What Is the Role of Surgery? (ID 1830)
14:15 - 15:45 | Author(s): D. Boffa
- Abstract
- Presentation
Abstract:
Surgical resection offers the best chance of cure for most patients with localized non-small lung cancer (NSCLC). However, the risk-benefit deliberation for surgery becomes less clear in patients with more locally advanced tumors (T4), because the procedures are typically more dangerous (higher risk) and the patient’s prognosis is worse (benefit less clear). That being said, surgery remains a curative option for a significant proportion of patients with T4 tumors. In order to minimize risk and maximize benefit, surgeons should select patients with 1) T4 tumors that can be removed safely, 2) T4 tumors that can be completely removed (R0) and 3) patients that are less likely to experience early systemic failure. The group of T4 NSCLC tumors that have historically been amenable to safe surgical resection include those that invade the spine, trachea, esophagus great vessels, and atrium. The 7[th] edition of the lung cancer stage classification system expanded the T4 designation to include tumors that involve a nodule in a separate ipsilateral pulmonary lobe. The recently released proposal for the 8[th] edition of the lung cancer stage classification system has moved tumors greater than 7cm in maximum diameter and tumors that invade the diaphragm to the T4 category. We have previously stated that changes in staging nomenclature should NOT be taken as justification for changing the way a patient is treated (because the revision only considers prognosis without any regard to treatment). However, these additional members of the T4 staging group pose the same risk-benefit conundrum that the others members pose and are discussed. Global health should be assessed as this is a critical component to the surgical risk calculation for patients. This typically includes an assessment of comorbid condition severity, pulmonary function testing, exercise testing and cardiopulmonary stress testing in patients at risk for cardiac disease. Strategies for safe removal of T4 tumors typically center around preparation for the unexpected. The supporting services should be alerted to not only the planned elements of the case but also possible needs in the event of a more extensive resection. The anesthesia team should be prepared to deal with abrupt bleeding (e.g. appropriate intravenous access that is located away from vessels that are likely to be clamped), the need for alternate ventilation strategies (e.g. jet ventilation). Any surgical specialty that could support an extended resection (e.g. spine service) should be alerted to the possibility. Surgeons should adjust their surgical approach to not only address what is apparent, but possible occult involvement of neighboring structures. Incisions should be placed in a way that allows the surgeon the flexibility to extend the planned resection. If possible, entrance should preserve tissues that can be used to treat surgical complications (e.g. preserving muscle for later use as a muscle flap). The exposure should allow for proximal and distal control of neighboring vessels, the use of cross table ventilation and the urgent use of cardiopulmonary bypass. Complete resection (removing all gross and microscopic disease) is of paramount importance, as the survival of patients is severely compromised by a positive surgical margin. While positive margins are an unfortunate reality to cancer surgery, every effort should be made to estimate the likelihood that a negative surgical margin can be obtained. At times this involves an exploratory phase of the resection (occasionally a minimally invasive approach to start) in order to assess the extent of local involvement (because imaging is notoriously inaccurate for determining the extent of local invasion). Finally the multi-disciplinary team must attempt to select patients that are less likely to develop early systemic failure, as these patients will not benefit from resection. This is of course not knowable with any degree of certainty but an estimate is helpful. Patients should undergo a thorough staging evaluation (brain imaging, PET scanning). While not an absolute contraindication for surgical resection, surgeons should be cognizant of other staging parameters that further compromise the patient’s potential for long-term survival. Most notably this would include the patient’s mediastinal lymph node status. The presence of mediastinal lymph node metastases (N2) is a further indication of the patient’s risk for systemic failure, and is an overall poor prognosticator. While prognosis does not alone define treatment, the patient’s overall prognosis should be considered when attempting to justify surgical risk (which is typically increased for T4 tumor resection). For this reason, it is recommended that surgeons refrain from resecting of T4 tumors associated with N2 disease as their default approach, and rather develop a strategy that attempts to allow patients to declare their potential for early failure. One strategy would be to offer the patient curative-intent nonsurgical therapy (chemoradiation) and observe the patient for a “local only” recurrence. In conclusion, surgical resection of T4 tumors is reasonable and effective in highly selected NSCLC patients. The onus is on surgeons and multidisciplinary care teams to attempt to identify the patients most likely to benefit and least likely to be harmed by surgery.
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GR01.04 - Salvage Surgery After Definitive Chemoradiation Therapy (CRT) (ID 1831)
14:15 - 15:45 | Author(s): E. Vallieres
- Abstract
- Presentation
Abstract:
After definitive CRT, approximately 25-30% of patients with stage III disease will fail at their primary site while the regional and systemic fields are under control. As a result, the question of whether some of these patients may potentially benefit from salvage resection of their primary site is often brought up at multidisciplinary tumor boards. The largest published series is from Duke who reported earlier this year on 31 patients in 17 years who underwent lobectomy after definitive radiation therapy (RT), 29 of whom had also received concurrent chemotherapy. Median dose of RT was 60Gy, ranging from 40 to more than 70. The median interval in between completion of the RT and the lobectomy was 18 weeks, ranging from 8 to 111. The majority of these resections were done open though, to their credit, 6 were done VATS without conversion. There was no operative mortality and 48% patients experienced some complications, only a third of these being major. There were no post op bronchopleural fistulae (BPF) despite only a third of patients having their stumps covered: 30/31 achieved an R0 resection, 19/31 had viable tumor in the specimen as histological confirmation of recurrence / persistent disease was not mandated before resection. Median follow-up (f-up) was 26 months and the median OS was 60 months: 20 months if persistent tumor was present in the resected specimen. For the patients who went to salvage resection for recurrent disease (n=3: DFIs being 240, 300 and 700 days) the OS was 9 months, significantly less than the 26 months of those who had persistent disease after RT. The 5 y survival was 31%, 0 if N1-2 disease was present at resection or if salvage was done for relapse, but very small numbers… (1) In 2013, the Yale group reported on 14 patients in 6 years who underwent salvage resection for biopsy proven persistent/ recurrent T disease after definitive CRT. Most underwent lobectomies (9), 2 pneumonectomies. 36% underwent stump coverage. There was no mortality at 90 days, 43% experienced some complication, including 1 ARDS and I BPF. Median post op survival was 9 months, mean 2 year survival was 49%.(2) Bauman in 2008 reported on 24 patients in 8 years who underwent salvage resection after RT, mean dose of 64 Gy (59 to 70), 22 had received concurrent chemo. The interval from completion of RT to surgery ranged from 5 to 94 weeks (median 21). Most underwent lobectomies but 10 were pneumonectomies, including 4 right sided. 19/24 had stump coverage, 16 by omentopexy. Median OR time was 5.5 hours. There was one post op death due to ARDS, 58% experienced some complications, no BPF. 80% of specimen had viable tumor, 2 had R1 resections, 11/24 had N1-2. Median f-up was 29 months, median OS was 30 months, 43 months if PET information/changes led to salvage resection. The estimated 3 year survival was 47%: 2 patients had were found to have brain metastases within 2 months of the salvage resection, neither had had brain imaging in the re-evaluation leading to salvage surgery.(3) Personal opinion (4): the preoperative evaluation of such candidates should always include fresh CT PET, brain MRI and PFTs including a DCO as well as a quantitative perfusion scan as the possibilities of pneumonectomy are not insignificant in this population. Smoking cessation is mandatory. The location of the tumor at presentation also matters: it may be technically much more difficult to perform a lobectomy for centrally radiated lesions. Though not the topic at hand, in my experience, the technical challenges to salvage after SABR pale in comparison as usually the hilar structures are relatively intact after SABR. These surgeries can be challenging and I would encourage that one obtain as much information as possible upfront before going to resection. This includes that one attempt to obtain histological confirmation of viable cancer before undertaking these surgeries. We now know that after RT, particularly after SABR, the PET information may be falsely positive. Along the same lines, I will get EBUS sampling of the mediastinal and hilar lymph nodes before resection. If negative, I will add mediastinoscopy evaluation even in those who had mediastinoscopy at presentation. (5) Intraoperatively, you need to communicate with anesthesia that these patients do not tolerate excess IV fluid well at all as a result of having had their mediastinum radiated. We prepare/ harvest the intercostal muscle bundle at entry. Early circumferential control of the proximal PA and PVs early on is also favored… just in case. Intrapericardial access to the PVs often helps when the hilum is fibrosed, in such instances, open division of the lobar bronchus will often help accessing the lobar PA branches, particularly with the RUL. We cover all of our stumps with the prepared intercostal bundle. Post-operatively, IV fluid restriction remains a priority. Patients whose left hilar dissection was difficult are kept fasting until the left recurrent nerve function is evaluated or judged to be intact. Any concern prompts immediate laryngoscopic evaluation and temporary medialization of any suspicious “lazy” vocal cord follows. The literature on the topic is sparse and all retrospective but we can conclude from its review that: in experienced hands, such resections can be performed safely with acceptable morbidity, such resections, particularly if one is attempting to perform less than a pneumonectomy can be technically challenging and that selection of the patients who may benefit the most from such surgery is not easy. References: Yang CJ, Meyerhoff RR, Stephens SJ, et al. Long-Term Outcomes of Lobectomy for Non-Small Cell Lung Cancer After Definitive Radiation Treatment. Ann Thorac Surg 2015; 99:1914–20 Kuzmik GA, Detterbeck FC, Decker RH, et al. Pulmonary resections following prior definitive chemoradiation therapy are associated with acceptable survival Eur J Card-Thorac Surg 44 (2013) e66–e70 Bauman JE, Mulligan MS, Martins RG, et al. Salvage Lung Resection After Definitive Radiation (>59 Gy) for Non-Small Cell Lung Cancer: Surgicaland Oncologic OutcomesAnn Thorac Surg 2008;86:1632–9 Page B, Blitz M, Louie BE, et al. Pulmonary Resection of NSCLC can be performed safely following definitive chemoradiotherapy. Oral presentation 13th World Conference on Lung Cancer, San Francisco, CA August 1[st] 2009, J Thorac Oncol. 4(9) Supplement 1:S301, September 2009 Louie BE, Kapur S, Farivar AS, et al. Safety and Utility of Mediastinoscopy in Non-Small Cell Lung Cancer in a Complex Mediastinum, Ann Thorac Surgery 92(1): 278-83, 2011
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ORAL 35 - Surgical Approaches in Localized Lung Cancer (ID 155)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 8
- Moderators:M. de Perrot, J. Mitchell
- Coordinates: 9/09/2015, 16:45 - 18:15, 601+603
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ORAL35.01 - Surgical Approach and Disease Recurrence in NSCLC Patients in the MAGRIT Study (ID 318)
16:45 - 18:15 | Author(s): E. Vallieres, M. Zielinski, E. Stoelben, Y. Wu, J. Fu, K. Costas, M. Takenoyama, S. Hazelrigg, J. Wang, C. Chen, M. Higashiyama, D. Harpole, R. Shen, D. Rice, R. Malthaner, W. Lai, G. Leschber, F. Tanaka, S. Yau, N. Mesaros, M. Debois, C. Debruyne, K. Langfeld, P. Therasse, T. Vanakesa
- Abstract
- Presentation
Background:
Surgical resection is the standard treatment for early stage Non-Small Cell Lung Cancer (NSCLC). Anatomical resection with lymphadenectomy is recommended in surgically treated patients with Stage I-IIIA NSCLC. Whether mediastinal lymph node dissection (MLND) or mediastinal lymph node sampling (MLNS) should be performed remains controversial, and there is currently no consensus within the literature. We describe surgical approaches and patterns of disease recurrence in patients enrolled in MAGRIT: a large global randomized study of the MAGE-A3 Cancer Immunotherapeutic versus placebo after complete tumor resection (Phase III trial, MAGRIT, NCT00480025).
Methods:
Study participants were aged ≥18 years, with histologically-proven, MAGE-A3-positive Stage IB, II or IIIA NSCLC (AJCC 6.0) who had undergone R0 anatomic resection of their tumor (lobectomy or pneumonectomy) with mediastinal lymphadenectomy. Patients were randomized to MAGE-A3 or placebo in a 2:1 ratio. A total of 2,272 patients were treated at 556 centers in 34 countries. Because MAGRIT did not demonstrate efficacy overall, and because the number of recurrences in the placebo arm was small (n=271), recurrence patterns by surgical technique are presented in the overall population. An analysis of the placebo population was also conducted as the overall population results are subject to potential bias (a limited treatment effect in small sub-groups cannot be excluded). Cox regression models were used to explore whether lymphadenectomy procedure could be prognostic for disease-free survival (DFS) or overall survival (OS).
Results:
In the total treated population, 76% were men, 52% had squamous cell carcinoma, and 52% received adjuvant chemotherapy. More than half (57%) of patients were enrolled in Europe, with 23% in East Asia, 16% in North America and 4% in other countries. 47% of patients had Stage IB, 6.5% IIA, 30% IIB, and 17% IIIA disease. Lobectomy (including bi- and sleeve-lobectomy) was performed in 85% of patients, and 14% required pneumonectomy. MLNS was performed in 53% and MLND in 47% of patients. MLNS and MLND patients had a similar disease stage distribution. By region, the percentage of patients who underwent MLNS was: 36% in Europe, 65% in East Asia, 94% in North America and 59% in other countries. Among patients who had undergone MLNS or MLND, 37% (n=447/1202) and 36% (379/1067) developed recurrent disease, respectively. Loco-regional recurrence was observed in 40% (177/447) of patients after MLNS and 31% (118/379) after MLND, with distant recurrence observed in 55% (244/447) and 64% (244/379), respectively. There was no difference in the pattern of distant metastases between patients who had MLNS or MLND. Cox modeling showed no impact of the extent of lymphadenectomy on either DFS or OS. A separate analysis of patients in the placebo arm demonstrated similar trends to those of the total study population.
Conclusion:
Lobectomy (including bi- and sleeve-lobectomy) was the most frequently used treatment for patients who participated in the MAGRIT study. Important regional differences in lymphadenectomy were observed. Although the patterns of recurrence varied to some extent with the type of lymphadenectomy, our study did not demonstrate any prognostic impact related to the type of lymphadenectomy performed.
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ORAL35.02 - Wedge Resection vs Segmentectomy for Patients with T1A N0 Non-Small Cell Lung Cancer (ID 3208)
16:45 - 18:15 | Author(s): C.J. Yang, D.Y. Chan, B.C. Gulack, P.J. Speicher, M.W. Onaitis, B.C. Tong, T.A. D'Amico, D. Harpole, M.F. Berry, M.G. Hartwig
- Abstract
- Presentation
Background:
A previous study of the Society of Thoracic Surgeons database showed that non-anatomic resection had lower perioperative morbidity than segmentectomy for non-small cell lung cancer (NSCLC); however the study lacked long term outcomes. We tested the hypothesis that segmentectomy for stage T1a N0 NSCLC had better long-term survival than wedge resection using the U.S. National Cancer Data Base (NCDB).
Methods:
Perioperative outcomes and overall survival (OS) of patients with clinical T1a N0 NSCLC who underwent wedge resection or segmentectomy in the NCDB from 2003-2011 were assessed using propensity-score-matched analysis. Groups were matched for common prognostic covariates (year of diagnosis, race, sex, age, education, income, insurance status, facility type, distance from facility, Charlson/Deyo comorbidity score, tumor size and location). Additional propensity-matched analyses were performed on patients with tumors ≤ 1 cm, patients with no comorbidities, and patients with pathologic T1a pN0 disease.
Results:
Of 40,058 clinical stage T1a N0 NSCLC patients, wedge resection and segmentectomy were performed in 7,517 (19%) and 1,268 (3%) patients, respectively. After matching, all baseline covariates, including comorbidity scores, were balanced between the wedge (n=1,231) and segmentectomy (n=1,231) groups. There were no significant differences between wedge and segmentectomy regarding 30-day mortality (1.6% [n=20] vs 1.5% [n=18], p=0.94). However, wedge was associated with significantly lower long-term survival than segmentectomy (Figure 1); this finding remained consistent even in a propensity-matched analysis of patients with tumors ≤ 1 cm (5 year OS: 56.8% [wedge] vs 78.2% [segmentectomy], log-rank p<0.01). To minimize treatment selection bias due to comorbidities, a propensity-matched analysis was also performed between wedge (n=509) and segmentectomy (n=509) for patients without comorbidities; wedge resection was associated with worse survival when compared with segmentectomy (5 year OS: 65.5% vs 69.5%, log-rank p<0.01). An additional propensity-matched analyses demonstrated that wedge (n=1,099) was associated with worse survival when compared with segmentectomy (n=1,099) for patients with pathologic T1a pN0 disease (5 year OS: 56.8% vs 65.5%, log-rank p<0.01).Figure 1
Conclusion:
In an analysis of a population-based dataset, a large proportion of patients was found to have received wedge resection for stage T1a N0 NSCLC. Segmentectomy for T1a N0 NSCLC had similar 30-day mortality but improved long-term survival when compared to wedge resection, even for patients with very small tumors ≤ 1 cm, for patients with no comorbidities and for patients with pathologic T1a pN0 disease.
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ORAL35.03 - Salvage Surgery for Local Failures after Stereotactic Ablative Radiotherapy for Lung Malignancies (ID 626)
16:45 - 18:15 | Author(s): N. Verstegen, A. Maat, F. Lagerwaard, M. Paul, M. Versteegh, J. Joosten, W. Lastdrager, E. Smit, B. Slotman, J. Nuyttens, S. Senan
- Abstract
- Presentation
Background:
Stereotactic ablative radiotherapy (SABR) is a guideline-recommended therapy for unfit patients with early stage non-small cell lung cancer (NSCLC), and for pulmonary metastases. Experience with SABR for potentially operable patients is also increasing, and salvage surgery may have a role in patients who subsequently develop a local tumor recurrence. However, prior high-dose SABR could theoretically increase local adhesions and compromise wound healing. As the published literature is limited, we describe our experience with salvage surgery in 17 patients who developed a local recurrence after SABR.
Methods:
Patients who underwent surgical salvage for a local recurrence following SABR for pulmonary malignancies were identified from two Dutch institutional databases, as well as cases provided by other Dutch surgeons. Complications were scored using the Dindo-Clavien-classification.
Results:
Seventeen patients who underwent surgery for a local recurrence were identified. Patients were treated with SABR for either primary non-small cell lung cancers (N=9) or solitary metastasis (N=8). Four patients with solitary metastasis underwent surgery twice each for separate recurrences. Median time to local recurrence was 15.6 months. Recurrences were diagnosed with CT- and/or [18]FDG-PET-imaging, with 5 patients also having a pre-surgical pathological diagnosis. Extensive adhesions were observed during 5 resections, requiring conversion from a thoracoscopic procedure to thoracotomy in 3 procedures. Four patients experienced complications post-surgery; grade 2 (N=2) and grade 3a (N=2), respectively. All resected specimens confirmed the presence of viable tumor cells. Median length of hospital stay was 7 days (range 4-15 days) and 30-day mortality was 0%. Lymph node dissection revealed mediastinal metastases in 3 patients, all of whom received adjuvant therapy. Median follow-up after surgery was 41 months and median overall survival was 38 months.
Conclusion:
Experience with 21 surgical procedures for local recurrences post-SABR revealed only two grade IIIa complications, and a 30-day mortality of 0%. Median overall survival after surgery was 38 months. These results suggest that salvage surgery may be safely performed in selected patients following SABR.
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ORAL35.04 - Discussant for ORAL35.01, ORAL35.02, ORAL35.03 (ID 3374)
16:45 - 18:15 | Author(s): D.R. Jones
- Abstract
- Presentation
Abstract not provided
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ORAL35.05 - The Role of Surgical Mediastinal Resection in CT Screen-Detected Lung Cancer Patients (ID 960)
16:45 - 18:15 | Author(s): R. Flores, D. Nicastri, T. Bauer, R. Aye, S. Andaz, L. Kohman, B. Sheppard, W. Mayfield, R. Thurer, R. Korst, M. Straznicka, F. Grannis, H.I. Pass, C. Connery, R. Yip, J.P. Smith, D.F. Yankelevitz, C.I. Henschke, N. Altorki
- Abstract
- Presentation
Background:
Comparison of long-term survival of patients with clinical Stage I non-small-cell lung cancer (NSCLC) with and without mediastinal lymph node resection (MLNR) in the International Early Lung Cancer Action Program, a large prospective cohort in a low-dose CT screening program.
Methods:
All instances of thoracic surgery for first solitary primary non-small-cell lung cancer prompted by low-dose CT screening, performed under an IRB approved common protocol at each of the participating institutions since 1992 to 2014, are included. Follow-up time was calculated from diagnosis to death from lung cancer, last contact, or December 31, 2014, whichever came first. Univariate logistic regression analysis of the demographic, CT, and surgical findings for those with and without MLNR was performed. Kaplan-Meier (K-M) survival rates and Cox regression analysis was performed using all significant univariate variables.
Results:
The 10-year Kaplan-Meier (K-M) NSCLC-specific survival rate for the 225 patients manifesting as a subsolid nodule was 100%, regardless of whether they had MLNR (N = 169) or not (N = 56). For the 373 NSCLC patients manifesting as a solid nodule, for those who had MLNR (N = 285) and those who did not (N = 88), the K-M NSCLC-survival rate was not significantly different (86 % vs. 93%, P = 0.23). The rate was 95% vs. 96% (P = 0.86) for those whose pathologic tumor diameter was <= 10 mm; 83% vs. 94% (P = 0.19) for 11-20 mm, and 79% vs. 86% (P = 0.67) for 21-20 mm. Cox regression analysis comparing MLNR with no MLNR showed that survival rates were not significantly different (P = 0.33), but significantly survival decreased when the tumor diameter was above 20 mm (HR= 5.1, 95% CI: 1.6-15.7).
Conclusion:
Lymph node evaluation is not necessary for resection of subsolid nodules in patients with screen-detected lung cancer.
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ORAL35.06 - Limited Resection for Non-Small Cell Lung Cancer Referring to Pathology (ID 216)
16:45 - 18:15 | Author(s): M. Yano, J. Yoshida, Y. Fujii
- Abstract
- Presentation
Background:
Precise preoperative diagnosis of the in-situ or minimally invasive carcinomas may identify patients that can be treated by limited resection. Though some clinical trials of limited resection for lung cancer have started, it will take much time to get results. We have reported a large scale data of limited resection at the previous WCLC meeting. We report here the data of subclass analysis according to the differences of pathology.
Methods:
Data from multiple institutions was collected on 1,737 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. As 11 patients without pathological diagnosis were excluded, 1726 patients were analyzed to determine the indication of limited resection in pathological differences. Disease free survival (DFS) and recurrence free proportion (RFP) were analyzed.
Results:
Median age was 63 years. Mean maximal diameter of the tumors was 1.4 ± 0.5 cm. DFS and RFP at 5 years were 91.0 % and 93.6 %, respectively. DFSs and RFPs at 5years in pathology were 92.2% and 94.7% in adenocarcinoma (n=1575), 76.3% and 82.4 % in squamous cell carcinoma (SqCC) (n=100), 100% and 100% in carcinoid (n=16), and 73.6% and 75.9 % in others (n=35). Adenocarcinomas were classified using 2 factors, the ratio of consolidation and tumor diameter (C/T) and tumor diameter into 4 groups, group A (C/T ≤ 0.25 and tumor diameter ≤ 2.0 cm), group B (C/T ≤ 0.25 and tumor diameter > 2.0 cm), group C (C/T > 0.25 and tumor diameter ≤ 2.0 cm), and group D (C/T > 0.25 and tumor diameter > 2.0 cm). DFSs and RFPs at 5 years were 96.7% and 98.8% in group A, 100% and 100% in group B, 89.2% and 92.3% in group C, and 76.7% and 77.8% in group D. In all groups of adenocarcinoma, the prognosis in patients who underwent segmentectomy was not superior to wedge resection.The prognosis in both groups A and B was good. These groups seemed to be good candidates of limited resection. The prognosis of group D were not good. Group D seemed not to be a good candidate of limited resection. Prognosis of group C was not bad, however, we could not conclude indication in group C because group C included both part solid tumors and solid tumors. In SqCC, tumor diameter was not prognostic factor and only segmentectomy was favorable prognostic factor (DFSs and RFPs in segmentectomy vs wedge resection: 78.2% and 85.5% vs 65.5% and 65.5%, respectively). In SqCC, there seemed to be indication of limited resection with segmentectomy. In carcinoid, all tumors except one were resected by segmentectomy. Segmentectomy for cT1 carcinoid seemed to be allowed. As prognosis in other pathologies was worse in limited resection, there seemed to be no indication of limited resection.
Conclusion:
Pathological diagnosis was important to determine the indication of limited resection. Measurement of tumor diameter and C/T was useful to determine the indication of limited resection for adenocarcinoma.
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- Abstract
- Presentation
Background:
General anesthesia with intubated ventilation is the standard in thoracic surgery. However, intubated anesthesia is often associated with postoperative discomfort and related complications. Recently, non-intubated anesthesia has emerged as a new option, but has only been assessed by several small-size reports. This study is to evaluate the feasibility and safety of non-incubated video-assissted thoracic surgery (VATS) for NSCLC under combined intravenous anesthesia (spontaneous respiratory status) and to compare it with the endotracheal intubated anesthesia.
Methods:
We retrospectively collected all NSCLC cases who underwent complete VATS lobectomy or segmental resection in our center under either non-intubated or intubated anesthesia. In this study, all non-intubated anesthesia cases were performed under combined intravenous anaesthetics plus analgesics while the intubated anesthesia cases were performed using double lumen endotracheal anesthesia. All procedures were conducted by the same group of surgeons and anesthesiologists from Dec 2011 to Dec 2014. Intra-operative and post-operative outcomes were compared between the two groups.
Results:
A total of 156 non-intubated and 188 intubated cases were included for analyses (Table 1). All non-intubated segment resections and the majority of non-intubated lobectomies were well exposed and were successfully completed; only 9 non-intubated cases planned for lobectomy (9/115, 7.2%) switched to intubated anesthesia. As shown in Table 2, both non-incubated lobectomy and segmentectomy had comparable outcomes with intubated anesthesia, regarding surgical duration, intraoperative blood loss, etc., as well as post-operative complications. Potential advantages were observed when comparing post-operative feeding time, volume of postoperative pleural drainage, and duration of post-operative hospital stay. Table1. Patient Demographics and Baseline Characteristics
Table2. Operative resultsSegmentectomy Lobectomy Intubated Non-intubated P- value Intubated Non-intubated P- value Age (years) 56.5±12.3 51.2±11.8 0.115 58.9±11.7 56.5±10.3 0.179 Sex(male,%) 11(44%) 12(35.3%) 0.087 97（58.4%） 64（55.2%） 0.215 Smoking 5(25) 7（20.6%） 0.161 21（12.7%） 15（13.0%） 0.679 BMI(kg/m2) 22.7±3.1 22.1±2.2 0.412 23.0±3.5 22.6±2.5 0.316 Tumor size 1.2±0.6 1.0±0.4 0.255 2.9±1.5 2.4±1.4 0.207 stage Ⅰ 25 32 108 87 Ⅱ 0 0 29 8 Ⅲ 0 0 26 20 Segmentectomy Lobectomy Intubated Non-intubated P- value Intubated Non-intubated P- value Surgical duration(min) 149.8±38.7 157.4±40.5 0.483 186.5±57.5 186.1±56.6 0.730 Intraoperative blood loss (mL) 83.6±64.1 73.9±56.5 0.076 154.7±258.3 130.8±185.7 0.165 Conversion to intubation 0 9 Postoperative feeding time (h) 13.9±4.6 7.6±3.2 <0.001 12.9±2.2 7.2±2.5 <0.001 Volume of pleural drainage (mL) 694.8±768.2 486.9±313.8 0.038 817.7±727.2 647.7±402.0 0.023 Chest-tube dwell time (days) 4.0±6.5 2.9±2.5 0.148 3.6±2.5 3.1±1.7 0.321 Duration of postoperative hospital stay (days) 9.5±7.4 7.1±3.5 0.041 8.8±4.1 7.6±2.4 0.044 Number of dissected lymph nodes 6.6±4.7 9.5±6.2 0.408 16.5±9.4 17.1±9.0 0.574 Stations of dissected lymph nodes 2.7±3.5 3.5±1.0 0.526 4.5±1.1 4.6±1.0 0.619
Conclusion:
This large comparative study demonstrated that complete VATS for resection of NSCLC under non-intubated anesthesia is feasible and safe. Non-intubated anesthesia is comparable to intubated approaches, and might have advanteages in terms of post-operative rehabilitation. However, the comparison regarding the long-term outcome is warranted.
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ORAL35.08 - Discussant for ORAL35.05, ORAL35.06, ORAL35.07 (ID 3375)
16:45 - 18:15 | Author(s): B. Passlick
- Abstract
- Presentation
Abstract not provided
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Author of
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-052 - Next Generation Exome Sequencing of Archival Lung Cancer Resection Specimens (ID 2159)
09:30 - 17:00 | Author(s): J. Mitchell
- Abstract
Background:
Genetic testing of non-small cell lung cancer has grown rapidly in recent years to accommodate expansion of the number of agents with molecular targets. Whole exome sequencing (WES) has been proposed as a method to comprehensively assess tumor mutation status that could replace current piecemeal approaches to predictive testing. The feasibility of WES for formalin fixed paraffin embedded (FFPE) clinical samples has recently been documented. However, several issues remain to be resolved before this platform can be adopted for routine clinical use. The purpose of the present study is to evaluate tissue coring as a method for obtaining DNA from FFPE tumor tissue, to assess the gene coverage of libraries prepared from FFPE, to determine how best to identify specific validated treatment targets, and to determine mutation load in clinical samples.
Methods:
We extracted DNA from 0.6 mm tissue cores selected both from tumor rich regions of paraffin blocks and normal lung tissue. DNA quality was assessed by Bioanalyzer and Qbit testing. A sequencing library was prepared using the Agilent Sure Select XT5 (v5) library kit. DNA was sequenced using an Illumina Hiseq 2500 ultrahigh throughput sequencing system. We used two flow cells for each of 4 samples to obtain a high level of coverage and to determine the effect of reducing coverage on mutation detection by computational methods. We used the DNA from non-tumoral regions to identify genomic polymorphisms and to then compile lists of mutations that were suspected of have a deleterious effect on the host. As a control, we tested DNA from each tumor by a clinically validated multiplexed panel (Illumina True Site panel). We compared our sequencing results with the TCGA database for the respective tumors.
Results:
DNA yield was 13 and 17 micrograms for the SCC and adenocarcinoma respectively. After shearing to 200 base pairs and library preparation, excellent quality DNA was obtained for sequencing. All of the mutations detected by Miseq analysis were detected by WES. Several mutations identified by WES have not been documented in TCGA. The mutations of the two tumors are sumarized below, including mutation load.WES Mutations SCC Adenocarcinoma Nonsynonomous SNV 247 51 Stopgain SNV 16 1 Fs deletion 10 1 Non-fs substitution 9 7 Fs insertion 2 2 Non-fs deletion 1 3 Non-fs insertion 1 0 Stoploss SNV 1 0 Splice region abnormality 9 0 Not present in TCGA 37 7 Present in TCGA 265 59 Mutations detected by Miseq TP53 (p.G245R) EGFR exon19 del CTNNB1 (p.S45C) Total (Mutation Load) 302 66
Conclusion:
This study confirms that WES is feasible on FFPE tissue and that the two tumors sequenced fall into the two categories, high and low mutation loads. The mutations identified include several that have not previously been reported. All mutations identified by high coverage clinical platforms were also detected by WES. WES may be suitbable for clinical application.
