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Laureano Molins

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    MS07 - Controversies with Stereotactic Radiation in Early Stage Lung Cancer (ID 70)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 6
    • Now Available
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      MS07.01 - Preoperative Optimazition: Reducing Surgery Complications Through Tobacco Cessation (Now Available) (ID 3474)

      14:00 - 15:30  |  Presenting Author(s): David Harpole

      • Abstract
      • Presentation
      • Slides

      Abstract

      Optimizing Outcomes after Pulmonary Resections with Smoking Cessation

      Data on increased risk of complications after major thoracic surgery for current smokers has been documented for several decades, suggesting that smoking cessation for even a few weeks may significantly reduce this risk based on early return of muco-ciliary clearance of respiratory secretions and decreased risk of atelectasis and pneumonia. Moreover, the awareness of potential lung cancer mortality on patients is a potent “teachable moment” for a smoking intervention. However, the literature is anything but definitive on:

      1. Method of smoking cessation / counseling (including pharmacological and non-pharmacological adjuncts)

      2. Length of time required for maximal risk reduction

      3. Durability of cessation after surgery

      This presentation will review the strongest trials in the literature, as well as recent data on a concerted risk reduction programs of Enhanced Recovery from surgery (ERAS) that include smoking cessation.

      References:

      Stokes SM, Wakeam E, Antonoff MB, Backhus LM, Meguid RA, Ordell D, Varghese TK. Optimizing health before elective thoracic surgery: systematic review of modifiable risk factors. J Thorac Dis 11: S537-554; 2109

      Sardari NP, Weyler J, Colpaert C. Prognostic value of smoking status in operated NSCLC. Lung Cancer 47:351-9; 2005

      Mills E, Eyawo O, Lockhart I. Smoking cessation reduces perioperative complications: A systematic review and meta-analysis. Am J Med 124:144-8; 2011

      Kozower BD, Lau CL, Philllips JV. Thoracic surgeon-directed tobacco cessation intervention. Ann Thorac Surg 89:926-30, 2010

      Thomasen T, Abrishami A, Yang Y. Interventions for perioperative smoking cessation. Cochrane Database Syst review 3:CD002299; 2014

      Lugg ST, Tikka T, Agostini PJ, Kerr A, Kalkat MS et al. Smoking and timing of cessation on postoperative complications after curative-intent lung cancer surgery. J Cardiothorac Surg 12:52-60; 2017

      Rodriguez M, Gomez-Hernandez MT, Novoa N, Jimenez MF, Aranda JL. Refraining from smoking shortly before lobectomy has no influence on the risk of pulmonary complications. Eur J Cardiothorac Surg 51:498-503; 2017

      Zaman M, Bilal H, Mahmood S, Tang A. Does getting smokers to stop smoking before lung resections reduce their risk? Interact Cardiovasc Thorac Surg. 14:320-323; 2012

      Gemine RE, Ghosal R, Collier G, Parry D, Campbell I, Davies G, Lewis KE. Longitudinal study to assess impact of smoking at diagnosis and quitting on 1-year survival for people with NSCLC. Lung Cancer 129:1-7; 2019

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      MS07.02 - Post SBRT Management: Surgery (Now Available) (ID 3475)

      14:00 - 15:30  |  Presenting Author(s): Mara Antonoff

      • Abstract
      • Presentation
      • Slides

      Abstract

      BACKGROUND:

      For early stage NSCLC, lobectomy and mediastinal lymph node dissection has been a long-standing, established standard of care. For patients unable to tolerate surgical resection, several single-institution studies have demonstrated SBRT to be an efficacious and well-tolerated treatment strategy.1-3 The RTOG-0236 trial, subsequently published in 2010, prospectively evaluated SBRT among patients at multiple North American centers, revealing high rates of local tumor control with acceptable treatment-related morbidity, which has been corroborated by other investigators with reproducibly acceptable rates of intermediate-term local control and minimal toxicities.4-6

      Given the success of using SBRT for Stage I NSCLC in medically inoperable patients, increasing interest has arisen regarding the potential application of this modality for healthier, potentially operable patients. In order to expand indications for use of this modality, important issues warranting investigation will include determination of the ideal means of following patients radiographically following SBRT as well as establishing protocols for intervention upon local failure. The outcomes for salvage lung resection following SBRT have been minimally reported. In this study, we aimed to evaluate our experience with operative lung resection in patients where SBRT has failed. Further, we review the combined outcomes in patients from our center along with those previously reported in the published literature.

      METHODS:

      We utilized our Departmental surgical database to identify all patients who underwent salvage pulmonary resection after prior radiation between January 2009 and September 2015. Among 716 patients who underwent pulmonary resection after previous radiotherapy, 21 met inclusion criteria, and these patients comprised the study cohort (MDACC group). Detailed patient data were retrospectively collected from our departmentally maintained, prospectively entered database and supplemented with additional chart review.

      In addition, a MEDLINE search was performed to identify all previous reports of surgical resection following local failure after initial treatment with SBRT. This resulted in 56 articles, which were reviewed to specifically identify publications regarding lung resection following local recurrence after SBRT. Four studies were identified, totaling 18 patients; however, as one report7 included resection of specimens lacking any residual disease, we used only the other 3 reports for cumulative analyses.8-10 From these previous publications, data were extracted for each patient and were combined with those of the MDACC cohort, thus constituting the final aggregate cumulative group.

      Student’s paired t-tests were used to compare pre-SBRT and pre-salvage surgery pulmonary function test results. Kaplan Meier analyses were performed in order to evaluate survival from the time of surgery as well as survival from completion of SBRT.

      RESULTS:

      At our institution, 21 individuals met inclusion criteria and comprised the MDACC group, and the cumulative group included 37 patients at 4 institutions. Baseline details regarding histology, sex, age, and medical operability are included in Figure 1. Elements of the radiation treatment received are also shown in Figure 1.

      Salvage surgery was performed at a median of 16 months following completion of SBRT, with a range of 6.4 to 104 months. Extent of resection is shown in Figure 1. Three (8.1%) operations were performed via minimally invasive approaches (2 thoracoscopic and 1 robotic-assisted). Adhesions were noted intraoperatively for nearly all (36/37, 97.3%) patients. Final pathology resulted in upstaging for 9/15 (60%) of patients in the MDACC group.

      Early postoperative outcomes were available for the 21 patients in the MDACC group (Figure 2). Two (9.5%) required post-operative admission to the intensive care unit (ICU), and stayed for a median of 5.5 days. Pulmonary complications were most common, occurring in 7 (33.3%) patients. Two (9.5%) patients had a prolonged air leak and 2 (9.5%) patients were discharged home on oxygen.

      During follow-up of the 21 MDACC patients, 5 developed recurrence. The three-year cumulative incidence of distant recurrence was 23.8%, with all recurrences distant and median time to recurrence 36.2 months. The median disease-free survival among MDACC patients was 19.2 months. Median survival from surgery for the MDACC group was 46.9 months, with 3-year survival of 53.2%. Thirty- and 90-day mortality were both 1 (4.8%). In the cumulative group, median survival was also 46.9 months and 3-year survival was 71.8%.

      CONCLUSIONS:

      Our findings demonstrate that resection following local failure of SBRT in highly select individuals is feasible, safe, and has an overall acceptable morbidity and mortality, albeit higher than what is typically observed in non-irradiated patients. In considering salvage resection, we 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 multi-disciplinary tumor board setting. Further studies are clearly warranted to establish treatment algorithms for those patients who demonstrate locally persistent or recurrent disease following SBRT and to clinically characterize the most appropriate operative candidates.

      abstract figures .jpgreferences image.jpg

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      MS07.03 - Post SBRT Management: vs Radiation (Now Available) (ID 3476)

      14:00 - 15:30  |  Presenting Author(s): Marco Trovo

      • Abstract
      • Presentation
      • Slides

      Abstract

      Stereotactic Body Radiation Therapy (SBRT) represents the standard of care for medically inoperable patients affected by early-stage Non-small cell lung cancer. Numerous phase I/II and retrospective studies have reported very high rates of local-progression free survival, ranging from 85% to 100% at two years. Interestingly, these data are reproducible among the published series, despite their heterogeneity. Severe lung toxicity (Grade ≥3 lung toxicity) is low, excluding centrally located tumor, ranging from 0% to <10%.

      Because of the following factors: 1) Very high local control rate, 2) very low clinical toxicity rate, 3) fragility of the treated population, the assessment of the response after SBRT has not be considered crucial in the patient management. Recently the perspective changed. Due to the excellent results in terms of local control, the publications of several paper that documented a superior outcome of SBRT vs. limited lung resection, and comparable data vs. lobectomy, more medically operable patients and less fragile populations have been treated in recent years. Moreover prospective trials on operable patients have been conducted. It is implicit that for operable patients the evaluation of a possible failure after SBRT is mandatory to guide further local (or systemic) therapies. Most patients with recurrent disease after SBRT will succumb to progressive cancer if left untreated. Although this is a frail patient population with competing risk of death, lung cancer specific mortality remains crucial. Even though chemotherapy might improve survival, the majority of patients are unfit to receive cytotoxic chemotherapy. However this scenario is going to be completely changed by the arrival of “immune-therapy” due to the overall favorable toxicity profile.

      The ESTRO-ACROP consensus guideline on implementation and practice of SBRT for early-stage NSCLC were recently published (1). Patient follow-up according to published guidelines is a mandatory component of any SBRT protocol. A frequency of 3-6 months in CT of the thorax is suggested, at least for the first year, thereafter the frequency might be tailored to whether the patient is medically operable or not. Three major items are considered of crucial importance when conducting the follow-up of the patient for the correct interpretation of follow-up images: 1) knowledge of the patterns of lung injury after SBRT; 2) detailed knowledge of the SBRT dose distribution, 3) knowledge of the pattern of failure.

      The discrimination between malignant lesion and post-radiation pneumonitis or fibrosis is often challenging. Both the radiation oncologist and the radiologist must be aware of the radiological patterns

      of SBRT-induced lung injury and of their relative frequency. This will become of crucial importance as SBRT is employed for treatment of operable patients, who can eventually benefit from salvage surgery for local relapse. The pattern of changes in lung parenchyma on CT post-SBRT can generally be categorized as acute (within 6 months) or late (after 6 months). Several patterns were described both for early and late radiographic changes (2).

      The differential diagnosis between local recurrence and fibrosis appear to be challenging in those patients who develop pattern characterized by dense consolidation and diffuse fibrosis. Such patterns can be classified as mass-like and modified conventional pattern, as we showed. Those patterns occur in about 74–76% of the cases. Patients who relapse have lesions that enlarged during the follow-up. Thus, a PET/CT in cases of enlargement of the lung fibrosis may be reliable in the differential diagnosis between recurrence and lung injury. FDG-PET imaging is considerate mandatory in case of suspected local recurrence on CT images, but it should be considered only optional during regular follow-up. Biopsy confirmation of suspected local failure is recommended only in patients who are likely to undergo salvage therapy if recurrence is detected. We share the idea of Huang and colleagues, who proposed an algorithm for follow-up of patients who are candidates for salvage therapies (3).

      1. Guckemberger M, Andratschke N, Dieckmann K, et al. ESTRO ACROP consensus guideline on implementation and practice of stereotactic body radiotherapy for peripherally located early stage non-small cell lung cancer. Radiother Oncol 2017;124:11-17.

      2. Trovo M, Linda A, El Naqua I, Javidan-Nejad C, Bradley J. Early and late lung radiographic injuries following stereotactic body radiation therapy (SBRT). Lung Cancer 2010;69:77-85

      3. Huang K, Dahele M, Senan S, et al. Radiographic changes after lung sterotactic ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A systemic review of the literature. Radiother Oncol 2012;102:335-342.

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      MS07.04 - Stage I (Resectable) NSCLC: Surgery (Now Available) (ID 3477)

      14:00 - 15:30  |  Presenting Author(s): Ryota Tanaka

      • Abstract
      • Presentation
      • Slides

      Abstract

      Lobectomy and lymph node dissection have been the standard therapeutic procedure for localized lung cancer since Cahan’s “Radical lobectomy” was published in 1960 [1]. In 1995, the Lung Cancer Study Group (LCSG) published findings from a randomized controlled study of clinical stage T1N0 non-small cell lung cancer (NSCLC), [2] that showed inferior overall survival and ~3× local recurrence rate in the limited (sublobar; segmentectomy or wedge) resection arm compared with the lobectomy arm. Although the LCSG study had some flaws (30% of patients had tumors >2 cm; wedge resections without lymph node dissection were performed as limited resections; inclusion of non-peripheral NSCLC in the limited resection arm, which could cause higher local recurrence rates), its results suggested that lobectomy is the superior option.

      Lobectomy has since been adopted worldwide as the surgical standard of care, whereas the indication for segmentectomy to treat lung carcinomas with solid appearances on computed tomography (CT) is controversial, although several non-randomized studies have suggested that survival and recurrence may be equivalent between lobectomy and sublobar resection (SLR) in patients with smaller lesions (≤ 2 cm) [3,4]. Improvements in imaging technology, such as thin-section CT (TSCT), have led to more patients who present with localized, early-stage lung cancers; and increased detection of small, peripheral NSCLC has renewed interest in SLR as an alternative to lobectomy. In addition, tumors with ground-glass opacity (GGO) have been correlated with less-invasive pathological findings of lepidic adenocarcinoma (AD) growth. Therefore, these patients may be feasible candidates for SLR. The Japan Clinical Oncology Group (JCOG) conducted a cohort study of early peripheral lung cancer (JCOG0201) and investigated the use of TSCT criteria to diagnose non-invasive lung AD, to preoperatively predict pathological non-invasive cancers [5]. Following this observational study, three ongoing trials (JCOG0804/WJOG4507L, JCOG1211 and JCOG0802/WJOG4607L) were initiated to confirm the validity of limited resection for stage I lung cancers, stratified according to preoperative TSCT findings. A non-randomized phase III trial (JCOG0804/WJOG4507L) was conducted to evaluate the efficacy and safety of SLR for peripheral GGO-dominant small lung cancers (tumor diameter ≤ 2.0 cm) and with consolidation tumor ratio ≤ 0.25, based on TSCT [6]. Five-year relapse-free survival (RFS) was 99.7% (95% CI: 97.7–100.0%), with no local recurrences. This study showed SLR (mainly wedge resection) to provide sufficient local control and RFS for peripheral GGO-dominant lung cancer (as seen on TSCT). A randomized phase III trial (JCOG0802/WJOG4607L) was conducted to compare overall survival after segmentectomy with that of lobectomy in patients with peripheral small (≤ 2 cm) NSCLC lesions [7]. The ongoing Cancer and Leukemia Group B (CALGB) 140503 trial is another large, multicenter randomized trial to compare disease-free survival between SLR and lobectomy among patients with peripheral small (≤ 2 cm) NSCLC lesions [8]; and is similar to the JCOG0802/WJOG4607L trial. However, as CALGB 140503 allows wedge resection as a surgical intervention, the JCOG0802/WJOG4607L trial offers a more definitive comparison of segmentectomy vs lobectomy for small invasive AD. The JCOG0802/WJOG4607L trial completed enrolling 1106 patients in 2014 and will clarify whether limited resection for primary lung cancer is not only function-preserving but also curative. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines recommend segmentectomy or wedge resection for patients with insufficient pulmonary reserve or with other major comorbidities, and for patients with tumors ≤2 cm that are either (a) pure AD in situ (AIS) confirmed by histopathological analysis, (b) nodules with ≥50% GGO on CT, or (c) confirmed by radiologic surveillance to have long doubling times (≥400 days) [9]. However, we need the results from all prospective randomized trials to form new treatment strategies for early-stage lung cancers.

      References

      [1] Cahan WG. Radical lobectomy. J Thorac Cardiovasc Surg 1960;39:555-72.

      [2] Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995;60:615-22.

      [3] Tsubota N, Ayabe K, Doi O, et al. Ongoing prospective study of segmentectomy for small lung tumors. Study Group of Extended Segmentectomy for Small Lung Tumor. Ann Thorac Surg 1998;66:1787-90.

      [4] 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;132:769-75.

      [5] 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;6:751-6.

      [6] Suzuki K, Watanabe S, Wakabayashi M, et al. A nonrandomized confirmatory phase III study of sublobar surgical resection for peripheral ground glass opacity dominant lung cancer defined with thoracic thin-section computed tomography (JCOG0804/WJOG4507L). J Thorac Oncol 2017;35(Suppl):abstr 8561.

      [7] 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;40:271-4.

      [8] Kohman LJ, Gu L, Altorki N, et al. Biopsy first: Lessons learned from Cancer and Leukemia Group B (CALGB) 140503. J Thorac Cardiovasc Surg 2017;153:1592-7.

      [9] Ettinger DS, Wood DE, Akerley W, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016. J Natl Compr Canc Netw. 2016;14:255-64.

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      MS07.05 - Stage I (Resectable) NSCLC: Radiation (Now Available) (ID 3478)

      14:00 - 15:30  |  Presenting Author(s): Suresh Senan

      • Abstract
      • Presentation
      • Slides

      Abstract

      For patients with a peripheral stage I NSCLC, the non-surgical treatment of choice is stereotactic ablative radiotherapy (SABR). Patients who are fit to undergo surgery, but instead undergo SABR, have a 3-year overall survival ranging from 76-86% [Siva S, Oncologist 2016], which is superior overall survivals in medically unfit patients treated using SABR. In 2013, the ESMO Clinical Practice Guidelines recommeded that surgery ‘should be offered to patients with stage I or II NSCLC who are willing to accept procedure-related risks’ [Vansteenkiste J, Ann Oncol 2013]. In the absence of completed randomized clinical trials of surgery versus SABR, a number of recent propensity score matched analyses have been performed. A pooled meta-analysis of propensity score matched data showed no significant differences in cancer specific survival between the two local treatments [Chen H, IJROBP 2018].

      Changes in the treatment patterns for patients with early-stage NSCLC have be reported in a number of countries, all showing an increase in the utilization of SABR in mainly elderly patients [Damhuis R, Ann Oncol 2019; Holmes JA, JNCI Ca Spectrum 2017]. These findings are in part due to the increase in the frail elderly presenting with lung cancer, and to the growing awareness of treatment-related mortality in this population. For example, data from the US National Cancer Database revealed that differences in 30- and 90-day post-treatment mortality between surgery and SABR increased as a function of age, with the largest differences in favor of SABR observed among patients older than 70 years [Stokes WA, JCO 2018[.

      Ongoing and future randomized studies comparing both modalities will also have to take account of the view of patient preferences. This is illustrated by recent randomized trial of surgery versus SABR (SABRTOOTH, ISRCTN13029788), in which 84 high-risk patients were approached by pulmonologists and oncology nurses for study participation, and 24 (29%) were randomized [Franks K, WCLC 2018]. The main reason for declining study participation was patient preference with 29% preferring surgery and 42% SABR. Overall 9 patients (38%) did not receive their randomized treatment. Of 7 patients who had been randomized to surgery but not undergoing surgery, 6 received SABR, 1 radical radiotherapy. Similarly, of 2 patients randomized to SABR, but who did not undergo SABR, 1 patient received radical radiotherapy, and another was lost to follow-up. Other research which may influence the ongoing debate are the effects of both local therapies on the immune system.

      The systemic inflammatory response induced after surgery can promote the emergence of tumors whose growth was otherwise restricted by a tumor-specific T cell response [Krall 2018]. SABR, on the other hand, is actively being investigated as an immunomodulator to enhance systemic anticancer effects [Marciscano AE, IJROBP 2019], with a randomized placebo-controlled trial of immune-checkpoint blockade underway in this population (NCT03833154).

      References

      Siva S. Curing Operable Stage I Non-Small Cell Lung Cancer With Stereotactic Ablative Body Radiotherapy: The Force Awakens. The Oncologist 2016;21:393–398

      Vansteenkiste J. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013 Oct;24 Suppl 6:vi89-98.

      Chen H. Stereotactic Ablative Radiation Therapy Versus Surgery in Early Lung Cancer: A Meta-analysis of Propensity Score Studies. Int J Radiat Oncol Biol Phys 101:186-194, 2018

      Damhuis R. Annals of Oncology (2019) 30 (suppl_2): ii26-ii30. 10.1093/annonc/mdz064

      Holmes JA, JNCI Cancer Spectrum, Volume 1, Issue 1, September 2017, https://doi.org/10.1093/jncics/pkx003

      Stokes WA. Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer. J Clin Oncol2018 Mar 1;36(7):642-651.

      Franks K. SABRTOOTH: A Feasibility Study of SABR Versus Surgery in Patients with Peripheral Stage I NSCLC Considered to be at Higher Risk for Surgery. Proceedings of WCLC 2018 P2.16-16

      Marciscano AE. Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities. In press Int J Radiat Oncol Biol Phys 2019 https://doi.org/10.1016/j.ijrobp.2019.02.046

      Krall JA. The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy. Sci. Transl. Med. 10, eaan3464 (2018)

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      MS07.06 - Hot Topics in SBRT - Biopsy, Central Lesions, Radiologic Evaluation (Now Available) (ID 3479)

      14:00 - 15:30  |  Presenting Author(s): Cecile Le Pechoux  |  Author(s): Angela Botticella, Antonin Levy, Olivier Henry, Isabelle Chabert, CAROLINE Caramella

      • Abstract
      • Presentation
      • Slides

      Abstract

      Stereotactic body radiotherapy (SBRT) has taken a growing place among treatment strategies in lung cancer in the past ten years because of its reported good results and favourable risk-benefit ratio especially in high-risk patients. This treatment modality allows delivering precisely a very high dose of radiation therapy to a targetable lesion, using a small number of fractions (3 to 5 more frequently). It has become the standard of care in medically inoperable peripheral early stage non-small cell lung cancer (NSCLC) patients. It is also frequently used in metastatic patients to treat cranial as well as extra-cranial metastases. Recently small randomised studies evaluating SBRT in oligometastatic NSCLC have shown promising results. Its role is now well accepted however there are situations where SBRT is still a subject of controversy and may be regarded as a hot topic

      because of the lack of pre-treatment biopsy

      because of less favourable outcome in central lesions and higher risk of complications

      because of the difficulty of radiologic evaluation

      When a peripheral lung nodule is discovered, suspect of being lung cancer, attempt should be made to obtain a pathological diagnosis before any treatment is proposed. Percutaneous CT–guided transthoracic biopsy is the established investigation in the work-up of pulmonary nodules, but there is a risk of complications such as pneumothorax (20-40%). However in patients with poor lung function (severe COPD, emphysema..), tissue sampling can be particularly challenging especially when the nodule is beyond the reach of conventional bronchoscopy. These are typically the patients that may be considered for SBRT, possibly presenting a contra-indication to transthoracic biopsy. Criteria for definition of a nodule as lung cancer without biopsy confirmation have been proposed such as progressive growth on CT imaging or presence of a hypermetabolic lesion on PET scan, and multidisciplinary tumor board consensus on the clinical diagnosis of lung cancer; there should be at least a 85% risk of malignancy, based upon accepted criteria [Postmus; Louie, Reid].

      If stereotactic radiotherapy in peripheral early NSCLC is presently a standard of care in inoperable patients due to co-morbidities and age, its role is more controversial for centrally located tumors because of less favorable outcome and higher risk of complications. In the past years, there has been a need to better classify these patients differentiating ultra-central from central lesions. The RTOG 0813 phase I/II trial, evaluated dose escalation in 120 patients with centrally-located non-small lung cancer with a five-fraction schedule that ranged from 10 to 12 Gy per fraction [Bezjak 2019]. The maximum tolerated dose was 60 Gy (5 fractions of 12 Gy), which was associated to a 2 year local control rate of 87.9%. They reported a fatal hemoptysis rate of 4%, potentially attributable to stereotactic radiotherapy [Bejzak 2015]. Even if the authors of this prospective study reported that outcome was comparable with that of patients with peripheral early-stage tumors, the risk of severe toxicity seems to be higher than in peripheral tumors. In another prospective phase II study, the Nordic hilus trial, which included 74 patients with central tumors within 1 cm from the proximal bronchial tree (PBT), the administered dose was 8 fractions of 7 Gy [Lindberg]. The authors reported a grade 4-5 toxicity of 19% among patients with tumor close to the main bronchus (ultra-central location) versus 3% in patients with tumor close to a lobar bronchus (central location). In a retrospective study of 88 patients with ultra-central lesions defined as tumors abutting PBT or trachea, or close to esophagus, a grade 3 toxicity or higher was reported in about 20% patients [Wang]. In another smaller retrospective study, where patients received 12 fractions of 5 Gy, outcome was quite good but toxicity ≥ grade 3 was reported in 38% of patients [Tekatli]. Thereby stereotactic radiotherapy for ultra-central tumors cannot be considered a standard treatment and more studies are needed for all central tumours to find the optimal dose regimen.

      Radiological evaluation after SBRT is performed mostly with chest CT scan, and changes occurring early and/or late are very common but can be tricky for radiologists as well as clinicians [Ronden,Febbo]. If FDG PET-CT is well established as staging tool prior to treatment, it is generally not used for surveillance. It may be useful though to differentiate local recurrence from radiation-induced lung opacity. Ideally, a treatment failure suspicion should be confirmed with a biopsy.

      These hot topics regarding SBRT show the difficulty to include patients into prospective trials; efforts have been made and should be pursued.

      References

      Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28(suppl_4):iv1-iv21.

      Louie AV, Senan S, Patel P, et al. When is a biopsy-proven diagnosis necessary before stereotactic ablative radiotherapy for lung cancer?: A decision analysis. Chest 2014; 146(4):1021-1028.

      Reid M, Choi HK, Han X et al. Development of a Risk Prediction Model to Estimate the Probability of Malignancy in Pulmonary Nodules Being Considered for Biopsy. Chest 2019. [Epub ahead of print]

      Lindberg K, P.Bergström, OT Brustugun et al. The Nordic HILUS-Trial - First Report of a Phase II Trial of SBRT of Centrally Located Lung Tumors. J Thorac Oncol 2017;12(15) Abstract S340.

      Bezjak A, Paulus R, Gaspar LE, et al. Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non-small-cell lung cancer: NRG Oncology/RTOG 0813 trial. J Clin Oncol 2019;37(15):1316-1325.

      C. Wang, B. Sidiqi, E. Yorke, et al. Toxicity and local control in “ultra-central” lung tumors treated with SBRT or high-dose hypofractionated RT. J Thorac Oncol 2018; 13(10).

      Tekatli H, Haasbeek N, Dahele M, et al. Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with "Ultracentral" Non-Small Cell Lung Cancer. J Thorac Oncol 2016;11(7):1081-1089.

      Ronden MI, Palma D, Slotman BJ, Senan S. Brief Report on Radiological Changes following Stereotactic Ablative Radiotherapy (SABR) for Early-Stage Lung Tumors: A Pictorial Essay. J Thorac Oncol 2018;13(6):855-862.

      Febbo JA, Gaddikeri RS, Shah PN. Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Primer for Radiologists. Radiographics 2018;38(5):1312-1336.

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    MA20 - Thymic Tumors: From Molecular to Clinical Results and New Challenges in Other Rare Thoracic Tumors (ID 149)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
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      MA20.07 - Thymomectomy and Total Thymectomy or Simple Thymomectomy for Early Stage Thymoma Without Myasthenia Gravis: An ESTS Thymic Working Group Study (Now Available) (ID 1683)

      11:30 - 13:00  |  Author(s): Laureano Molins

      • Abstract
      • Presentation
      • Slides

      Background

      Resection of thymic tumors has traditionally included removal of the tumor and the thymus gland (thymothymomectomy). Nevertheless, in recent years, some authors questioned the need to remove the thymus gland in non-MG thymomas, suggesting that resection of the tumor (simple-thymomectomy) is enough from an oncological point of view in Stage I (TNM stage classification) thymoma patients. The aim of our study was to compare short- and long-term outcome of thymothymomectomy vs. simple-thymomectomy using European Society of Thoracic Surgeons (ESTS) Thymic Database.

      Method

      We investigated 1131 patients with thymic epithelial tumors included in the ESTS-Thymic Database. Three-hundred twenty-four clinical stage I (cT1N0M0, according to the 8th edition of the UICC/AJCC TNM stage classification) without Myasthenia Gravis (non-MG) thymoma cases were evaluated from 23 contributing centers (2000-2017), of which 300 (93%) thymothymomectomy and 24 (7%) simple-thymomectomy. Surgical upstaging was evaluated. In pathological stage I, we compared the completeness of resection, the rate of complications, the 30-day mortality, the overall survival and the disease-free survival (DFS).

      Result

      Overall, we observed an upstaging to stage III in 10 (3%) patients. We did not observe any significant difference between the two techniques in terms of the completeness of resection, the rate of complications and the 30-day mortality. The 5-year overall survival rate was 94% in the thymothymomectomy group and 56% in the simple-thymomectomy group (Figure 1 - P= 0.0004). The 5-year DFS was 95% in the thymothymomectomy group and 82% in the simple-thymomectomy group (Figure 1 -P= 0.013).

      figure 1.png

      Conclusion

      Patients affected by stage I TNM non-MG thymoma submitted to thymothymomectomy presented a significantly better DFS and overall survival than those submitted to simple-thymomectomy. Thymothymomectomy should be considered the procedure of choice in Stage I TNM non-MG thymomas, also considering the not negligible rate of pathological upstaging.

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    SH02 - Highlight of the Previous Day (ID 99)

    • Event: WCLC 2019
    • Type: Highlight of the Previous Day Session
    • Track:
    • Presentations: 1
    • Now Available
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      SH02.04 - Screening (Now Available) (ID 3665)

      11:30 - 13:00  |  Presenting Author(s): Laureano Molins

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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