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Y.W. Kim
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MS 24 - Management of GGO-Containing Nodule (ID 546)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Radiology/Staging/Screening
- Presentations: 5
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MS 24.01 - Natural History of GGO-Containing Tumors (ID 7754)
14:30 - 14:50 | Presenting Author(s): Ryutaro Kakinuma
- Abstract
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Abstract:
The natural history of GGO-containing tumors, i.e., subsolid nodules (SSNs), is a major concern not only in CT lung cancer screening, but in daily clinical practice. SSNs are classified into pure ground-glass nodules (GGNs) and part-solid GGNs on the basis of their consistency. SSNs are classified according to their status as transient or persistent. Articles in the literature related to the natural history or long-term follow-up results of SSNs are summarized in Table. In the largest CT lung cancer screening cohort reported to date, nonsolid nodules (synonymous with pure GGNs) and part-solid nodules were detected in 4.2% (2392 of 57,496) and 5.0% (2892 of 57,496), respectively, of the participants at baseline (Table). The numbers of SSNs reported in the articles ranged from 19 to 3433 (median, 139). The median follow-up periods ranged from 1.1 years to 12 years (median, 2.9 years). The percentages of pure GGNs that grew ranged from 3% to 58% (median, 15%). The percentages of lung cancers among the SSNs ranged from 1% to 71% (median, 7%). An inherent limitation of studies of the natural history of SSNs is that not all of the SSNs are pathologically confirmed. The changes in persistent SSNs on sequential thin-section CT images in the Research Center for Cancer Prevention and Screening (RCCPS) examinations have tentatively been classified into six types; increasing type, stable type, decreasing type, fluctuating type, sudden onset type, and overtaking type. Some of the SSNs were evaluated on the basis of semiautomatic volumetry. Although the natural history of SSNs had gradually been clarified, the complete natural history of SSNs as a whole remains unknown. In the current era of ultralow-dose chest CT at a chest x-ray equivalent dose, a lifelong follow-up study should be considered.
Footnotes. ¶ SSN, subsolid nodule; * PGGN, pure ground-glass nodule; ** PSN, part-solid nodule; n/a, not available. † This study did not report the numbers of pure and part-solid GGNs separately. ≠ Growth was calculated by comparing actual mass to mass when first detected and is expressed as a percentage. $ A synonym of PGG.; ^ Baseline; ^^ Annual repeat screening. ø Follow-up period of the “grew” group. [1 ]Among the 1764 cases in which the nonsolid nodules were stable or growing, the median time to pathologic diagnosis was 1.7 years; the median follow-up time in the cases without a pathologic diagnosis was 1.4 years. [2] The median time from the initial identification of the nonsolid nodules to pathologic diagnosis was 1.2 years; the median follow-up time in the cases without a pathologic diagnosis was 1.7 years. [&] This study did not report the number of SSNs that grew and number of stable SSNs separately. ***HGGN, heterogeneous GGN. [3] Among the 2325 cases in which the PSNs were stable or growing, the median time to pathologic diagnosis was 0.5 years; the median follow-up time in the cases without a pathologic diagnosis was 1.1 years. [4] The median time from the initial identification of the PSN to pathologic diagnosis was 0.8 years; the median follow-up time of 0.7 years for cases without pathologic diagnosis. § Fifty-seven patients had stopped receiving follow-up examinations after a median of 5.6 years because of the presence of stable disease in 42 and reduced disease in 15. # Forty-five patients were continuing to undergo follow-up examinations, and their median follow-up period was 12 years; 40 were stable and 5 showed growth.SSNs¶ Grew Lung Cancer Author Journal Year Total Consistency,n Follow-up Period (yr.) n (%) n (%) Kodama Ann Thorac Surg 2002 19 PGGN*, 19 Median, 2.7 11 (58) 5 (26) Hiramatsu J Thorac Oncol 2008 125 PGGN, 95 Median, 2.9 14 (15) 8 (6) PSN**, 30 12 (40) Silva J Thorac Oncol 2012 76 PGGN, 48 Mean, 4.2 8 (17) 4 (5) PSN, 28 12 (43) Takahashi Jpn J Radiol 2012 150 PGGN, 150 Mean, 5.5 19 (13) 8 (5) Chang Chest 2013 122 PGGN, 122 Mean, 4.9 12 (10) 11 (9) Kobayashi J Thorac Oncol 2013 108 PGGN, 82 Median, 4.2 29†(27) 25 (23) PSN, 26 Matsuguma Chest 2013 174 PGGN, 98 Mean, 2.4 14 (14) 53 (30) PSN, 76 27 (36) Lee Respir Med 2013 175 PGGN, 143 Median, 3.8 28 (20) 26 (15) PSN, 32 18 (56) Attina Radiol Med 2013 146 PGGN, 140 Mean, 2.3 41 (29) 5 (3) PSN, 6 6 (100) Kim Ann Thorac Surg 2013 139 PGGN, 69 Mean, 3.7 2 (3) 7 (5) PSN, 70 21 (30) Tamura J Thorac Oncol 2014 63 PGGN, 63 Mean, 2.2 29 (46) 45 (71) Eguchi Lung Cancer 2014 124 PGGN, 124 Median, 4.8 64 (52) 32 (26) Scholten Eur Respir J 2015 117 PGGN, 69 Median, 7.9 33≠ 28 (24) PSN, 48 46≠ Kakinuma Radiology 2015 439 PGGN, 439 Median, 6.0 45 (10) 4 (1) Silva Diagn Interv Radiol 2015 95 PGGN, 95 Median,1.7ø 18 (19) n/a Yankelevitz Radiology 2015 2877 Nonsolid$,2392^ Median[1] 1764[&] 84 (3) Nonsolid,485^^ Median[2] 163[&] Lee Eur Radiol 2016 213 PGGN, 136 Median, 2.3 18 (13) 49 (23) PSN, 77 24 (31) Zhao Br J Radiol 2016 70 PGGN, 62 Median, 2.1 6† (9) 5 (7) PSN, 8 Kakinuma J Thorac Oncol 2016 1231 PGGN, 1046 Mean, 4.3 116 (11) 85 (7) HGGN***, 81 23 (28) PSN, 104 45 (43) Cho J Thorac Oncol 2016 453 PGGN, 438 Median, 6.4 11 (3) 7 (2) PSN, 15 4 (27) Henschke AJR 2016 3433 PSN, 2892^ Median[3] 2325[&] 107 (3) PSN, 541^^ Median[4] 164[&] Sawada Chest 2017 226 PGGN, 166 §, # 39†(17) 124(55) PSN, 60 Mets Eur Radiol 2017 89 PGGN, 63 Median, 1.6 35†(39) n/a PSN, 26
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MS 24.02 - What Type of Surgery Should be Selected for GGO-Containing Tumors? (ID 7755)
15:10 - 15:30 | Presenting Author(s): Paul De Leyn | Author(s): Herbert Decaluwe, W. De Wever
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A ground glass opacity (GGO) is a radiographic finding defined as hazy, increased attenuation of the lung with preservation of bronchial vascular margin. A subsolid nodule (SSN) includes pure ground glass nodules and partsolid nodules in which both solid and ground glass components are present. These nodules are nowadays more commonly found with the introduction of CT screening programs. The optimal management of patients with SSN is of growing clinical concern. The newly (1) introduced adenocarcinoma classification makes a clear distinction between pre-invasive lesions (atypical adenomatous hyperplasia), adenocarcinoma in situ (AIS: ≤ 3cm pure lepidic growth without invasion), minimally invasive adenocarcinoma (MIA: ≤ 3cm lepidic growth with ≤ 5mm invasion) and invasive adenocarcinoma (IA) of different subtypes. Preinvasive lesions or MIA have an excellent survival and might be treated with sublobar resection. IA (especially certain subtypes) are more aggressive and should be treated with lobar resection combined with systematic nodal dissection. Pure GGO lesions can be non-specific inflammation, fibrosis or neoplasm. Recent guidelines (2) recommends for pure GGO nodules ≥6mm follow-up scan at 6 to 12 months and then every 2 years until 5 years. In a retrospective study (3) 83 patients with pure GGO lesion that had surgery and proved to be adenocarcinoma were described. 79,5 % were non IA and 20,5 % (IA). In a multivariate logistic regression analysis both preop GGO size on CT and pleural retraction were predictive factors for IA. Pure GGO lesions ≥ 10 mm should be resected if they persist or grow on follow-up CT. Partsolid nodules. When a nodule is partially solid or when in a GGO lesion a solid part appears, the risk of IA increases. In a prospective multicentric study Suzuki et al looked at radiologic criteria for predicting pathologic early (non-invasive) adenocarcinoma (4). In this study, the consolidation/tumor (C/T)ratio was measured in lung and mediastinal window settings. Radiologic non-invasive longadenocarcinoma could be defined as a subsolid nodule ≤2cm with a (C/T) ratio of 0.25 or less. Asamura et al (5) re-evaluated the radiology pathology correlation in this study in term of the prognosis. The radiologic criteria of a C/T ratio of 0.25 or less in tumor ≤3cm as well as 0.25 or less in tumors ≤2cm could be used to define a homogeneous group of patients with an excellent prognosis after surgery. These criteria can be used to select patients with early lung adenocarcinoma in which a sublobar resection (wedge or segmentectomy) would be safely indicated. For lesions with a tumor diameter of 2.0cm and a C/T ration >0.25 a prospective randomized fase III study comparing lobectomy and segmentectomy is ongoing (6). The incidence of N2 disease in clinical T1-T2N0 was evaluated (7). The incidence of unforeseen N2 disease was 1.5% in pure GGO lesions. N2 disease was found in 4.3% of semi solid tumors and 12.6% in pure solid tumors. In a multivariate analysis, tumors with any GGO components were less likely to have N2 disease (Odds ratio 0.14, 0.001). A recent study (8) used a nomogram for predicting the risk of IA in patients with solitary peripheral subsolid nodules. In a multivariate analysis the occurrence of IA was significantly correlated with lesion size, spiculation, vascular convergence and pleural tag. There are different subtypes of IA. The micropapillary and solid types are aggressive subtypes with a high rate of N2 (9). These types cannot be used for sublobar resection. Huang et al (10) analyzed histology obtained by CT guided needle biopsy or EBUS. Concordant subtyping of adenocarcinoma between the predominant pattern on resections and biopsy section was only observed in 58.6% of the cases. For high grade adenocarcinoma detection, preoperative biopsy had a low sensitivity (16.5%). So preoperative obtained histology cannot show us which type of resection we should perform. The degree of invasion is often overestimated in frozen section. However, frozen section has a high specificity for micropapillary and subsolid pattern (11). If this subtype is found during surgery by frozen section, lobectomy and lymph node dissection should be performed. Conclusion By modern imaging subsolid nodules containing GGO lesions are more often seen. When the C/T ratio is more than 50% there is a high risk of IA with certain subtypes which are very aggressive. These lesions should be managed by lobectomy and lymph node dissection until results from prospective studies are known. For lesions ≤2cm, with C/T ratio ≤25% wedge or segmentectomy can be the appropriate intervention. When a limited resection is performed, the margins and the lymph nodes should be examined by frozen section. 1.Travis WD, Brambilla E, Noguchi M et al. International Association for the Study of Lung cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol 2011;6:244-285 2.MacMahon H, Naidich D, Goo JM et al. Guidelines for management of incidental pulmonary nodules detected on CT images : from the Fleischner Society 2017. Radiology 2017;284:228-243 3.Moon Y, Sung SW, Lee KW et al. Pure ground-glass opacity on chest computed tomography: predictive factors for invasive adenocarcinoma. J Thorac Dis 2016;8:1561-1570 4.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 5.Asamura H, Hishida T, Suzuki K et al. Radiographically determined noninvasive adenocarcinoma of the lung : survival outcomes of Japan Vlinical Oncology Group 0201. J. Thorac Cardiovasc Surg 2013;146:24-30 6.Nakamura K, Saji H, Okada M 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 7.Gao SJ, Kim AW, Puchalsky JT et al. Indications for invasive mediastinal staging in patients with early non-small cell lung cancer staged with PET-CT. Lung Cancer 2017;109:36-41 8.Jin C, Cao J, Cai Y et al. A nomogram for predicting the risk of invasive pulmonary adenocarcinoma for patients with solitary peripheral subsolid lesions. J Thorac Cardiovasc Surg 2017;153:462-9 9.Hung JJ, Yeh YC, Wu YC et al. Factors predicting occult lymph node metastasis in completely resected lung adenocarcinoma of 3 cm or smaller. Europ J Cardio-Thorac Surg 2016;50:329-336 10.Huang KY, Ko PZ, Yao CW et al. Inaccuracy of lung adenocarcinoma subtyping using preoperative biopsy specimens. J Thorac Cardiovasc Surg 2017;154:332-9 11.Yeh YC, Nitadori JI, Kadota K et al. Using frozen section to identify histologic patterns in stage I lung adenocarcinoma ≤3 cm: accuracy and interobserver agreement. Histopathology 2015;66:922-938
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MS 24.03 - When to Operate GGO-Containing Tumors? (ID 7756)
15:30 - 15:50 | Presenting Author(s): David Harpole, Paul De Leyn
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With the advent of Chest CT screening, the identification of abnormalities has increased substantially. In addition to very small nodules of indeterminate significance, “ground glass opacities” (GGO) are often seen. Numerous series have been collected around the world attempting to define characteristics that predict the malignant potential of these GGOs. It is clear that a substantial fraction includes a component of invasive adenocarcinoma and warrant resection for cure prior to developing disseminated cancer. This presentation will review the literature for developing a rational algorithm for selection of those patients requiring which operation, as well as review outcomes. 1. Radiological determinants of malignancy using high-resolution CT and CT/PET 2. Criteria for patient section for resection or observation 3. Techniques for pre-resection localization for intraoperative identification of lesion 4. Appropriate selection lesions for extent of resection (lobe, segment or non-anatomic wedge) 5. Approach for resection 6. Outcomes after treatment Selected References Matsunaga T, Suziki K, Takamochi K, Oh S. What is the radiological definition of part-solid tumor in lung cancer? Eur J Cardiothorac Surg 2017; 51:242-247 Eguchi T, Kondo R, Kakkami S, Matsushita M, Yoshizawa A, Hara D, Matsuoka S, Tkeda T, et al. CT attenuation predicts the growth of pure GGO nodules Lung Can 2014;84:242-247 Suzuki K, Asamura H, Kusumoto M, Kondo H, Tsuchiya R. Early peripheral lung cancer: prognostic significance of GGO on thin section CT scan Ann Thorac Surg 2002;74:1635-9 Lee S, Leem C, Kim T, Lee K, Chung J, Jheon WS, Lee C. The long term follow-up of GGO detected on thin-section CT Respir Med 2013;107:904-10 Suzuki K, Shimohira M, Hashizume T, Ozawa Y, Sobue R, Mimura M, Mori Y, Ijima H, Watanabe K, Yano M, Yoshioka H, Shibamoto Y. Usefulness of CT-guided hookwire marking before VATS for small pulmonary lesions J Med Imag Rad Oncol 2014; 58:657-662. Mong-Wei L, Yao-Hui T, Yee-Fan L, Min-Shu H, Wei-Chun K, Jo-Yu C, Hsao-Hsun H, Yeun-Chung C, Jin-Shing C. Comuted tomography-guided patent blue vital dye localization of pulmonary nodules in uniportal thoracoscopy J Cardiovasc Surg 2016; 152:535-44 Fukui M, Suziki K, Matsunaga T, Oh S, Takamochi K. Surgical intervention for GGO-dominant lesions: observation or outright resection? Pan J Clin Oncol 2017;18:1-6 Cao C, Gupta S, Chandrakumar D, Tian D, Black D, Yan T. Meta-analysis of intentional sublobar resections versus lobectomy for very early stage non-small cell lung cancer Ann Cardiothorac Surg 2014; 3:134-141 Kodama K, Higashiyayma M, Tkami K, Oda K, Okami J, Maeda J, Koyama M, Nakayama T. Treatment strategy for patients with small peripheral lung lesions: Prospective study Eur J Cardiothoracic Surg2008; 34:1068-74 Yoshioka M, Ichiguchi O. Selection of sublobar resection for c-stage1A non-small cell lung cancer based on a combination of structural imaging by CT and functional imaging by FDG-PET Ann Thorac Cardiovasc Surg 2009; 15:82-8. Kohno T, Fujimoro S, Kishi K, Fujii T. Safe and effective minimally invasive approaches for small GGOs Ann Thorac Surg 2010; 89; 1114-7 Tsutani Y, Miyata Y, Nakayama H, Okurmura S, Adachi S, Yoshimura M, Okada M. Appropriate sublobar resection choice for GGO-dominant clinical stage 1A lung Adenocarcinoma Chest 2014; 145:66-71 Sook Y, Sung S, Mankoong M, Park K. The effectiveness of mediastinal node evaluation in a patient with GGO tumor J Thorac Dis 2016; 8:2617-2623 Wei S, Khao K, Guo C, Mei J, Pu Q, Ma L, Che G, Chen G, Wu Z, Wang Y, Kuo Y, Lin Y, Li W Lui L. Diagnosis and surgical treatment of lung GGO: a review of 663 cases. Sichan Da Xue Bao Yi Xue Ban 2017:48:359-362 Moon Y, Lee K, Moon S, Park J. Sublobar resection margin does not affect recurrence of clinical N0 non-small cell lung cancer presenting as GGO. World J Surg 2017;41:472-9 Hattori A, Matsunaga T, Takamochi K, Oh S, Suzuki K. Surgical Management of Multifocal Ground-Glass Opacities of the Lung: Correlation of Clinicopathologic and Radiologic Findings Thorac Cardiovasc Surg 2017; 65:142-14 Shimada Y, Saji H, Otani K, Maehara S, Maeda J, Yoshida K, Kato Y, Hagiwara M, Kakihana M, Kajiwara N, Ohira T, Akata S, Ikeda N. Survival of a surgical series of lung cancer patients with synchronous multiple ground-glass opacities, and the management of their residual lesions Lung Cancer 88 (2015) 174-180
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MS 24.04 - Possibility of Radiotherapy for GGO-Containing Tumors (ID 7757)
15:50 - 16:10 | Presenting Author(s): Hiroshi Onishi | Author(s): Y. Shioyama, Y. Matsumoto, K. Takayama, Yukinori Matsuo, A. Miyakawa, H. Yamashita, H. Matsushita, M. Aoki, K. Nihei, Tomoki Kimura, H. Ishiyama, N. Murakami, K. Nakata, A. Takeda, T. Uno, T. Nomiya, T. Takanaka, Y. Seo, Takafumi Komiyama, K. Marino, S. Aoki, K. Kuriyama
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Purpose/Objective(s): The popularization of computed tomography (CT) in clinical practice have increased a frequency of discovering ground-glass opacity (GGO)-containing tumor in lung. Surgery has been regarded as the general treatment including a purpose of histological examination for such tumors and its prognosis is better than that of solid-type tumors. Stereotactic body radiation therapy (SBRT) is a rapidly prevailing treatment modality in the radical treatment of mainly inoperable or high risk operable cases with stage I non-small cell lung cancer (NSCLC), but the most tumors treated with SBRT were solid type because SBRT has been performed principally for the pathology-proven tumors and it is generally difficult to acquire histological specimen in the tumors composed of GGO. Therefore a prognosis of the stage I NSCLC cases treated with SBRT when their tumors contained GGO has not been clear. The purpose of this presentation is to review the treatment outcomes for SBRT for the patients with GGO-containing tumor in our multi-institutional SBRT study group of Japanese Radiological Society (JRS-SBRTSG), and to discuss how we consider the validity of SBRT for them. Materials/Methods: GGO was defined as hazy opacity that does not obscure underlying bronchial structures or pulmonary vessels at high-resolution computed tomography. We have reviewed 174 patients (89 men, 85 women; mean age, 74 years) treated with SBRT whose lung tumor showed appearance of GGO accompanying solid component ratio to the whole tumor (S/T ratio) less than 50 % in diameter of the tumor and no metastases. SBRT was done because of the pathological proof, positive accumulation on PET study or growth of the tumor. In histology, 69 tumors were adenocarcinoma, 8 were squamous cell carcinoma, 5 were unclassified carcinoma and 92 cases were histology-unproven. The median tumor size was 23 mm (range, 9-53 mm). SBRT was performed using non-coplanar multiple static ports or dynamic arcs. A total dose of 40 -70 Gy (6-15 Gy / fraction) was prescribed in 4-10 fractions. Median biological effective dose (BED) was 108 Gy (range, 72-150 Gy) based on alpha/beta = 10 Gy. Survival, recurrence, and metastases rates were calculated using Kaplan-Meier method. Results: Median follow-up was 32 months. The 3-year local recurrence, regional lymph-node metastases, and distant metastases rates were 3.8%, 4.1%, and 8.6%, respectively. Mean S/T ratios of the subgroup with any recurrences and the subgroup with no recurrence were 22% and 4%, respectively. The rates of cause-specific and overall survival (OS) at 3 years were 98.1% and 85.6%, respectively. The 3-year OS rates of medically operable and inoperable subgroups were 96.2% and 85.6%, respectively. The 3-year OS rate of medically operable and histology-proven subgroup was 88.1%. The 3-year OS of female subgroup was 95.0% and it was significantly better overall survival rate than male. The treatment-related pneumonitis of grade 3 or more was observed in 3.4% of the total patients. Summary and Discussion: Natural course of GGO-containing tumor is much better than that of solid-type tumors. Sublober limited resection would be acceptable in the subgroup of stage I NSCLC if the tumor appears GGO for the most part because they have mostly no invasion nor metastases. SBRT is a so localized treatment only for the tumor that a study comparing SBRT versus limited surgery without regional lymph node resection might have a rationale of randomization for such candidates, however, we have to demonstrate the prognosis and risk factors regarding recurrence, survival, and late toxicity after SBRT with longer follow-up (more than 10 years). In conclusion, the outcomes of SBRT for patients with GGO-containing tumor (solid component was less than 50 % in total diameter) were excellent but some cases had local recurrence or metastases. GGO-containing in most of the tumor seldom produced local progression, lymph node metastases, or distant metastases after SBRT. Although more cases and longer follow up are mandatory, SBRT may be one of the radical treatment options for stage I NSCLC patients with GGO-containing tumor. We hope to have a further discussion regarding the validity of SBRT for them.
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MS 24.05 - Possibility of Chemotherapy for GGO-Containing Tumors (ID 7758)
14:50 - 15:10 | Presenting Author(s): Egbert F Smit | Author(s): Pieter E. Postmus
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The radiological term GGO or ground-glass opacity was established when high-resolution CT (HRCT) became part of standard practice, and describes “a hazy attenuation of lung, with preservation of bronchial and vascular margins: caused by partial filling of air spaces, interstitial thickening, partial collapse of alveoli, normal expiration, or increased capillary blood volume…” (1). As such GGO is a nonspecific finding but depending on the clinical circumstances it may suggest a specific diagnosis and have consequences for the diagnostic and therapeutic approach. Most primary lung tumours present with masslike areas of consolidation, however there are other patterns. A specific subtype of adenocarcinoma may present as GGO, and this was described as bronchioloalveolar carcinoma (BAC) (2). It reflects the unique lepidic growth pattern along the alveolar septa with a relative lack of acinar filling. The classification BAC was used for a broad spectrum of tumours including small non-invasive peripheral lung tumours, invasive adenocarcinoma with minimal invasion, mixed subtype invasive adenocarcinoma, mucinous and nonmucinous subtypes, and widespread disease. As in this larger group GGO is present in only a minority, it is difficult to conclude from the chemotherapy trials done specifically in BAC (3) what the efficacy of chemotherapy in tumours with as feature GGO is, nor has the pathological feature of lepidic growth been reported in these studies. Overall the response rate in BAC of single agents seems not to be different from other types of NSCLC. At a later stage, it seemed that gefitinib was especially effective in the non-mucinous subtype (4), in retrospect this might be explained by the molecular characteristics of both. EGFR mutation was more related to lepidic growth, whereas KRAS was especially found in mucinous types (5). It became clear that the term BAC leads to confusion and is representing a very heterogeneous group of tumours. It was therefore recommended to discontinue the use of the term BAC (6), and use a more descriptive classification based on histological findings. Within this new grouping the radiological description of ground-glass opacity was related to the pathological pattern of adenocarcinoma: pure GGO would favour adenocarcinoma in situ (AIS) or possibly minimally invasive adenocarcinoma (MIA), and GGO with a solid component > 5 mm in diameter would favour lepidic adenocarcinoma (7). The natural course of pure GGO or GGO with a small solid component is rather benign. In a large Japanese cohort followed for 4.3 + 2.5 years (mean) the frequency of change from pure GGO towards a - still small - solid component was found in 6.6% (69 out of 1046), of the cases initially diagnosed with a very small solid component change into part-solid nodules was seen in almost 20% (16 of 81) (8). All these observations come from resected tumours and cannot be diagnosed in small biopsies, this makes it difficult to characterize more advanced adenocarcinoma in the same way. The likely most GGO containing advanced tumours will be those diagnosed with (dominant) lepidic growth (9). Reports of chemotherapy efficacy are infrequent but do not show a real difference in sensitivity if treated with one of the commonly used regimens carboplatin – paclitaxel (10). Although the LACE-Bio study contains only small numbers of cases with lepidic growth, combining these patients with the ones with the prognostically less unfavourable histology (papillary, acinar) failed to demonstrate benefit of adjuvant chemotherapy (11). The frequency of finding more than one GGO (with or without a solid component) is rather high and reported as almost 30% (12). If this is in a patient with stage IV NSCLC it is questionable whether these are separate primaries or metastases. The behaviour of these lesions has not been systematically reported, personal observations confirm the rather indolent role of these lesions, usually without any pathological proof of malignancy, and no change during systemic therapy for an other stage IV tumour. The question whether the presence of GGO as such, either as part of the stage IV tumour or as a different lesion, should affect the choice of systemic therapy can not be answered. References: 1. Austin JHM, Müller NL, Friedman PJ et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 1996; 200: 327-331. 2. Jang HJ, Lee KS, Kwon OJ et al. Bronchioloalveolar carcinoma: focal area of ground-glass attenuationat thin-section CT as an early sign. Radiology 1996; 199: 485-488. 3. Miller VA, Hirsch FR, Johnson DH. Systemic Therapy of Advanced Bronchioloalveolar Cell Carcinoma: Challenges and Opportunities. J Clin Oncol 2005; 23:3288-3293 4. Cadranel J, Quoix E, Baudrin L et al. IFCT-0401 Trial. A Phase II Study of Gefitinib Administered as First-Line Treatment in Advanced Adenocarcinoma with Bronchioloalveolar Carcinoma Subtype. J Thorac Oncol. 2009;4: 1126–1135. 5. Yoshizawa A, Sumiyoshi S, Sonobe M et al. Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. J Thorac Oncol. 2013; 8: 52-61 6. Travis WD, Brambilla E, Noguchi M et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6: 244-85 7. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumours: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thor Oncol 2015; 10: 1243-1260. 8. Kakinuma R, Noguchi M, Ashizawa K et al. Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study. J Thorac Oncol 2016; 11: 1012-1028. 9. Travis WD, Asamura H, Bankier AA et al. The IASLC lung cancer staging project: proposals for coding T categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thor Oncol 2016; 11: 1204-1223. 10.Cadranel J, Gervais R, Merle P et al. Erlotinib versus carboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504. Eur Respir J 2015; 46: 1259–1261. 11. Tsao MS, Marguet S, Le Teuff G et al. Subtype classification of lung adenocarcinoma predicts benefit from adjuvant chemotherapy in patients undergoing complete resection. J Clin Oncol 2015; 33: 3439-3446. 12. Kim HK, Choi YS, Kim J et al. Management of Multiple Pure Ground-Glass Opacity Lesions in Patients with Bronchioloalveolar Carcinoma. J Thorac Oncol. 2010;5: 206–210.
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