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P.E. Van Schil

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    ED15 - Thymic Malignancies: Update on Treatment (ID 285)

    • Event: WCLC 2016
    • Type: Education Session
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 4
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      ED15.01 - Biology of Thymic Epithelial Tumors (ID 6506)

      14:30 - 15:50  |  Author(s): G. Giaccone

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      ED15.02 - Chemotherapy and Targeted Therapies of Thymic Malignancies (ID 6507)

      14:30 - 15:50  |  Author(s): N. Girard, C. Merveilleux Du Vignaux

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Thymic malignancies represent a heterogeneous group of rare thoracic cancers. The histopathological classification distinguishes thymomas from thymic carcinomas. Thymomas are further subdivided into different types (so-called A, AB, B1, B2, and B3) based upon the atypia of tumor cells, the relative proportion of the associated non-tumoral lymphocytic component, and resemblance to the normal thymic architecture. Thymic carcinomas are similar to their extra-thymic counterpart, the most frequent subtype being squamous cell carcinoma. The management of thymic epithelial tumours is a paradigm of multidisciplinary collaboration. The treatment strategy is primarily based on the resectability of the tumour. If complete resection is deemed not to be achievable upfront based on imaging studies, what is the case in Masaoka-Koga stage III/IVA tumors (classified as stage IIIA/IIIB/IVA in the 2015 IASLC-ITMIG TNM proposed system), after a biopsy is performed, primary/induction chemotherapy is administered, part of curative-intent sequential strategy integrating subsequent surgery or radiotherapy. Cases not eligible for local treatment receive definitive chemotherapy. Primary/induction chemotherapy is then standardin non-resectable advanced thymic epithelial tumors. Cisplatin-based combination regimens should be administered; combinations of cisplatin, adriamycin, and cyclophosphamide, and cisplatin and etoposide are the most usually used. Primary chemoradiotherapy with platin and etoposide is an option, especially for thymic carcinomas. Usually 2-4 cycles are administered before imaging is performed to reassess resectability of the tumor. Surgery should be offered to patients for whom complete resection is thought to be ultimately achievable; extended resection may be required. Hyperthermic intrapleural chemotherapy, as well as extra-pleural pneumonectomy may be discussed in case of stage IVA tumor. Postoperative radiotherapy is usually delivered. When the patient is not deemed to be a surgical candidate - either because R0 resection is not thought to be achievable, or because of poor performance status or co-existent medical condition, definitive radiotherapy is recommended part of a sequential chemoradiotherapy strategy. Combination with chemotherapy (including cisplatin, etoposide chemotherapy and a total dose of radiation of 60 Gy) may be considered as well. Chemotherapy should be offered as the single modality treatment in advanced, non-resectable, non-irradiable or metastatic (stage IVB) thymic epithelial tumor to improve tumor-related symptoms the aim is to improve tumor-related symptoms through obtention of tumor response, while prolonged survival is uncertain. Cisplatin-based combination regimen should be administered. No randomized studies have been conducted, and it is unclear which regimens are best; multi-agent combination regimens and anthracycline-based regimens appear to have improved response rates compared to others, especially the etoposide, ifosfamide and cisplatin combination. Combinations of cisplatin, adriamycin, and cyclophosphamide is preferred. Combination of carboplatin and paclitaxel is an option for thymic carcinoma. Surgery or radiotherapy is possible in rare and selected cases with unknown survival benefit. Recurrences of thymic epithelial tumors should be managed according to the same strategy as newly diagnosed tumors. Complete resection of recurrent lesions represents a major predictor of favorable outcome, and surgery is then recommended in case of resectable lesion. In non-resectable recurrences, several consecutive lines of chemotherapy may be administered when the patient presents with tumor progression. The re-administration of a previously effective regimen has to be considered, especially in case of previous response, late occurring recurrence, and for anthracyclins, a patient in a good medical condition and not having received cumulative doses precluding the safe delivery of at least 3 additional cycles. Preferred regimens for second-line treatment include carboplatin plus paclitaxel, and platin plus etoposide; capecitabine plus gemcitabine is an option. These regimens were evaluated in dedicated phase II trials. Options for subsequent lines include pemetrexed, oral etoposide. In patients with octreoscan-positive thymoma, not eligible to receive additional chemotherapy, octreotide alone or with prednisone may represent a valuable option. The use of targeted agents may be done in an off-label setting in advanced thymic malignancies. While KIT is overexpressed in 80% of thymic carcinomas, KIT gene mutations are found only in 9% of cases, consisting of mutations observed in other malignancies (V560del, L576P) or mutations unique to thymic carcinomas (H697Y, D820E). Responses and possibly prolonged survival was reported with the use KIT inhibitors - imatinib, sunitinib, or sorafenib - , mostly in single-case observations. Non-pretreated reported KIT mutants are not uniformly sensitive to imatinib, based on the clinical and/or the preclinical evidence in thymic carcinoma and/or other KIT-mutant malignancies. KIT sequencing (exons 9-17) is an option for refractory thymic carcinomas in the setting of possible access to off-label use of such inhibitors. KIT inhibitors also potently inhibiting other kinases, including Vascular Endothelial Growth Factor Receptors and Platelet-Derived Growth Factor Receptors activated in thymic malignancies. A phase II trial recently demonstrated the efficacy of sunitinib in terms of response and disease control rate in thymic epithelial tumors, including thymic carcinomas (ORR 26%; DCR: 91%) and, to a lesser extent, thymomas (ORR:6%; DCR:81%). Sunitinib may then represent an option as second-line treatment for thymic carcinomas, independantly from KIT status. There is no clinical data reporting on antitumor efficacy of other antiangiogenic drugs. mTOR is emerging as a potential target in thymic epithelial tumors, following tumor responses observed in phase I trials. Everolimus (10 mg daily) was evaluated in thymic epithelial tumors in a recently reported phase II trial reporting on a 22% response rate, as well as a 93% disease control rate. Everolimus may then represent an option for refractory tumors. Several trials assessing the efficacy of PD-1 checkpoint inhibitors are currently ongoing. A phase II study of pembrolizumab, a fully humanized IgG4 Ab that targets the PD-1 receptor, was recently reported; the study has accrued 30 patients. Four serious autoimmune disorders developed. Out of 30 patients evaluable for response so far the response rate is 24%. The off-label use of checkpoint inhibitors is currently not recommended. Overall, a dramatic improvement in our knowledge of the management of thymic tumors has occurred in the last few years. This improvement has primarily resulted from an increased interest in these rare tumors at some dedicated centers, and from the development of international efforts that succeed in putting together large-volume, top-quality centers all over the world, for databases, translational research, and clinical trials.

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      ED15.03 - Surgery of Thymic Malignancies (ID 6508)

      14:30 - 15:50  |  Author(s): M. Okumura

      • Abstract
      • Slides

      Abstract:
      Thymic epithelial tumors Thymic epithelial tumors are the most common malignancy among mediastinal tumors according to Japanese thoracic surgery survey (1). Surgical resection is generally the treatment of choice for thymic epithelial tumors. Thymic epithelial tumors are classified into thymoma, thymic carcinoma (TC), and thymic neuroendocrine carcinoma (TNEC). Retrospective surgical database of Japanese Association for Research of the Thymus (JART) revealed that recurrence free 10-year survival after macroscopic complete resection was 88% in thymoma, 51% in TC, and 11% in TNEC. Thymomas are further classified mainly into 5 pathological subtypes, WHO type A, AB, B1, B2 and B3. Pathological subtype of thymoma has been shown to reflect the oncological behaviors, and post-operative recurrence rate increases in this order. JART database study revealed that nearly 3 quarters of thymoma surgical cases have Masaoka stage I or II disease. Pleural dissemination is often encountered either before or after resection in thymoma while hematogenous or lymphatic spread seldom occurs. On the other hand, TC is often associated with metastasis to distant organs as well as nodal involvement in the mediastinum and cervical region. Approximately 3 quarters of surgically treated TC have Masaoka Stage III or IV disease in surgical cases. While most thymomas are treated by surgical resection, a considerable portion of TC are judged unresectable at initial presentation. TNEC often has nodal involvement. Initial resection is indicated when clinical diagnosis is a thymic epithelial tumor with Masaoka stage I or II. The standard procedure is extended thymectomy through median sternotomy even for tumors with Masaoka stage I or II disease because of the possibility of post-thymectomy myasthenia gravis, intrathymic metastasis and multiple foci of tumor. JART database study, however, revealed that recurrence rate in thymoma with T1N0M0 by UICC was not significantly different between two procedures, thymothymomectomy (1.4%) and thymomectomy (2.8%) (p = 0.192) (2). Furtheremore, systematic dissection of mediastinal lymph nodes is not supposed essential in thymoma because incidence of nodal involvement is negligible. Advancement in video-assisted thoracic surgery (VATS) has prompted endoscopic operation also for thymoma, and currently, partial resection of the thymus by VATS seems accepted for less-invasive thymoma when myasthenia gravis is not associated, but careful observation by annual examination by CT scan is recommended after partial thymectomy. Highly invasive thymomas should be treated by preoperative induction chemotherapy to reduce the tumor size. Pathological diagnosis by biopsy is required before chemotherapy to differentiate between invasive thymoma and TC. Resection of the pericardium, lung, great vessels, and thoracic wall is sometimes required. JART database study revealed that invasion of the thoracic wall was the independent factor of recurrence after complete resection. (3) Even subtotal resection sometimes results in long-term survival. If complete resection is not achieved, radiotherapy is supposed to control the remaining tumor. Surgery for thymoma with pleural or intrapericardial dissemination can be indicated. JART database study revealed that the number of the disseminated lesions is a prognostic factor and that patients with less than 10 lesions had better survival. (4) Operative procedure varies from partial pleurectomy to extrapleural pneumonectomy with resection of the primary lesion. The recommended procedure depends on the spread of disseminations. Although intrapericardial implantation is commonly thought to be hard to resect, resection can be achieved in some cases because thymomas usually do not invade into the heart muscle severely. Preoperative chemotherapy is supposed to enable complete resection of intrapericardial implantations through reduction of the tumor volume. Most of the hematogenous metastases of thymoma occur in the lung probably because the neoplastic cells can directly enter the blood stream through thymic veins. Surgical treatment for thymomas with lung metastasis is feasible, but indication of surgery for thymoma with extrathoracic distant metastasis should be determined carefully. Recurrence often occurs on the pleural surface followed by the lung metastasis. Surgical resection of the recurrent lesions in the intrathoracic cavity is generally thought to contribute to survival. (5) Preoperative induction therapy is almost mandatory in highly invasive TC and poorly-differentiated NEC. Concurrent chemoradiotherapy is effective in reducing the tumor size. Resection and reconstruction of even the ascending aorta under cardiopulmonary bypass can be attempted. Systematic mediastinal and cervical lymph node dissection is recommended because of high incidence of nodal involvement. Malignant germ cell tumors (GCT) Malignant GCT is a highly aggressive neoplasm arising in young males. Chemotherapy is recommended without pathological diagnosis when serum tumor marker is extraordinarily elevated. In case of non-seminomatous GCT, complete resection of the tumor after normalization of tumor marker value by chemotherapy should be achieved, or otherwise, tumor recurrence is highly possible. Resection and reconstruction of the great vessels under cardiopulmonary bypass is often necessary. Liposarcoma Mediatinal liposarcoma is a rare neoplasms and sometimes appears as a huge tumor. This neoplasm is supposed to be resistant to chemotherapy, and complete surgical resection is required. Local recurrence occurs frequently because obtaining safe surgical margin is difficult. Radiotherapy could be a treatment of choice for recurrent tumors. Lymphoid malignancies Role of surgery is limited. Surgical biopsy is sometimes required when ML is suspected by imaging and high value of serum sIL-2 receptor. When tumor remains after chemotherapy, surgical resection is sometimes indicated. Low-grade malignancy including MALT and Castleman’s disease can be exceptionally treated by initial surgery. References Committee for Scientific Affairs, The Japanese Association for Thoracic Surgery. Thoracic and cardiovascular surgery in Japan during 2013: Annual report by The Japanese Association for Thoracic Surgery. Gen Thorac Cardiovasc Surg. 2015 ;63:670-701. Nakagawa K, et al. Is thymomectomy alone Appropriate for stage I (T1N0M0) thymoma? Results of a propensity-score analysis. Ann Thorac Surg. 2016;101:520-6. Yamada Y, et al. Surgical outcomes of patients with stage III thymoma in the Japanese nation-wide database. Ann Thorac Surg 2015;100:961–7. Okuda K, et al. Thymoma Patients With Pleural Dissemination: Nationwide Retrospective Study of 136 Cases in Japan. Ann Thorac Surg 2014;97:1743–9. Mizuno T, et al. Surgical management of recurrent thymic epithelial tumors. A retrospective analysis based on the Japanese nationwide database. J Thorac Oncol. 2015;10:199–205.

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      ED15.04 - Radiation of Thymic Malignancies (ID 6510)

      14:30 - 15:50  |  Author(s): A. Rimner

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Radiation therapy (RT) plays an important role in the multimodality management of thymic malignancies. It can be employed in the neoadjuvant, adjuvant, definitive or palliative setting. Adjuvant RT is the most extensively studied setting for RT in thymic malignancies. After complete resection there is likely no role for adjuvant RT for patients with stage I thymomas, a possible role for patients with stage II thymomas, and likely a survival benefit in patients with stage III and IV thymomas. Several recent large database and population-based studies have detected a survival benefit for advanced thymomas, while the results for stage II thymomas have been mixed. For thymic carcinomas the impact of adjuvant RT appears more significant. Several large database and population-based studies have consistently reported a survival benefit with adjuvant RT for thymic carcinoma across various disease stages. For incompletely resected thymic tumors there is a stronger rationale for adjuvant RT based on emerging data and general oncologic principles. Neoadjuvant RT has been mostly explored in thymic carcinoma and demonstrated high response and operability rates. Definitive RT is an excellent treatment option for patients with unresectable thymic malignancies. While most thymic tumors are resectable, a subset of patients is technically or medically inoperable, due to invasion of critical structures or comorbidities. In general, thymic malignancies are radiosensitive, allowing for long-term local control rates. Palliative RT should be considered even in the recurrent or metastatic setting. Image-guided hypofractioned ablative RT may be used for oligometastatic disease as an alternative to surgical resection and has been shown to be a highly effective treatment modality with >90% long-term local control rates and minimal morbidity. Conventional palliative RT is an important modality to improve quality of life by alleviating pain, treating SVC syndrome, airway compression and other symptoms. Modern radiation therapy techniques such as 3D conformal radiation therapy or intensity-modulated radiation therapy should be used to minimize morbidity from treatment. Proton therapy may have advantages in certain clinical scenarios and is currently under investigation.

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    MTE05 - Where is the Place of Surgery for N2 Disease? (Ticketed Session) (ID 299)

    • Event: WCLC 2016
    • Type: Meet the Expert Session (Ticketed Session)
    • Track: Surgery
    • Presentations: 1
    • Moderators:
    • Coordinates: 12/05/2016, 07:30 - 08:30, Schubert 6
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      MTE05.01 - Where is the Place of Surgery for N2 Disease? (ID 6547)

      07:30 - 08:30  |  Author(s): P.E. Van Schil

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The diagnostic and management strategies for stage IIIA-N2 non-small cell lung cancer (NSCLC), which represents locally advanced disease with involvement of ipsilateral mediastinal lymph nodes, remain controversial despite results from several randomized controlled trials [1-2]. There are various reasons for this ongoing debate. First, stage IIIA-N2 represents a very heterogeneous patient population ranging from incidental discovery of positive N2 nodes during lung resection, to single mediastinal nodal involvement and bulky N2 disease where individual lymph nodes are hard to identify. In this setting, the precise diagnostic algorithm remains controversial. Currently, patients with proven or suspected lung cancer are mainly staged by integrated positron emission tomography – computed tomography (PET-CT). However pathological proof of nodal involvement should be obtained by a minimally invasive or invasive technique due to a relatively high rate of false positive nodes, owing to mainly inflammation [3]. Secondly, the optimal restaging strategy after induction therapy is heavily debated. Thirdly, specific controversy relates to the role of surgery versus radiotherapy and the precise extent of resection after induction therapy. Randomized trials included different subsets of N2 disease making the interpretation of results quite difficult. As a result of the limitations of available data heated discussions have been taking place for several decades on the optimal treatment strategy for this subset of patients. When N2 disease is detected during thoracotomy, this is referred to as incidental, unsuspected, unforeseen or “surprise” N2 [4]. When found intraoperatively, a resection should be performed as long as it can be complete. Adjuvant chemotherapy prolongs survival and is currently recommended in this setting. However the role of radiotherapy remains controversial and is currently evaluated in the randomized LungART trial (NCT00410683) [5]. In quite a large subgroup of patients, N2 disease is suspected on PET-CT scanning and subsequently confirmed by minimally invasive or invasive staging techniques. Although the term “potentially resectable N2” is often utilized, no precise, internationally accepted definition is available. Most patients in this sub-group will be treated by concurrent chemo-radiotherapy alone or induction therapy followed by surgery or definitive radiotherapy. Whether induction chemo-radiotherapy yields better results than chemotherapy alone was studied in the recently published, randomised trial NCT00030771 of the Swiss Cancer League [6]. No significant differences were found. However, this study was not adequately powered to show non-inferiority between the two strategies. There are different restaging techniques to evaluate response after induction therapy. In contrast to imaging or functional studies, remediastinoscopy provides pathological evidence but is technically more difficult and less accurate than mediastinoscopy done prior to induction treatment [3]. An alternative approach consists of the use of minimally invasive staging procedures to obtain an initial proof of mediastinal nodal involvement. Mediastinoscopy is subsequently performed after induction therapy to evaluate response [3]. In patients with proven mediastinal downstaging after induction who can preferentially treated by lobectomy, surgical resection may be recommended. Whether radiotherapy yields similar results has not been established yet. One of the reasons is that in patients undergoing chemo-radiotherapy pathology to evaluate response is not available making comparison with surgery quite difficult. A recent meta-analysis tried to better clarify the outcome of surgery compared to radiotherapy after induction treatment in patients with N2 disease [7]. Six trials including a total of 868 patients were included. Main outcome was overall survival. The authors concluded that when bimodality treatment is applied, both surgery and radiotherapy options are valid with a pooled hazard ratio for mortality in the surgery group of 1.01 (p not significant). In contrast, in trimodality regimens results support surgical resection as part of multimodality management with a pooled hazard ratio for mortality in the surgery group of 0.87 indicating a 13% relative improvement in overall survival (p= 0.068). In the recently published ESPATUE trial, patients with resectable stage IIIA-N2 and selected stages IIIB NSCLC were included [2]. No significant differences were found between the control arm consisting of induction chemotherapy followed by definitive chemo-radiotherapy, and the experimental arm administering induction chemotherapy followed by chemo-radiotherapy with a dose of 45 Gy, followed by surgical resection. Both treatment options are considered acceptable strategies for these highly selected patients with a relatively good prognosis. North American (American College of Chest Physicians 2013) [8] and European guidelines (European Society of Medical Oncology 2015) [1] recommend that in NSCLC patients with N2 involvement the treatment plan should be made with the input of an experienced multidisciplinary team. The ESMO guidelines include induction chemotherapy followed by surgery, induction chemoradiotherapy followed by surgery, or concurrent definitive chemoradiotherapy as possible treatment strategies for potentially resectable stage IIIA-N2 However bulky N2 disease is mostly treated with chemo-radiotherapy as these patients do not qualify for surgical resection due to extensive extracapsular involvement [1]. Furthermore complete resection, which is a major prognostic factor, is mostly not achievable in this subset of N2 disease. The standard of care in patients with good performance status is concurrent chemoradiotherapy [1]. Of particular interest to thoracic surgeons is the relatively new concept of “salvage” surgery after full-dose chemo-radiotherapy in stage IIIA-N2 NSCLC [9, 10]. These patients present with recurrent or progressive locally advanced disease, in some cases complicated by an infected cavity, rendering surgical resection technically difficult. Furthermore, a systematic nodal dissection may be challenging, especially when bulky lymph nodes were initially present. In conclusion, although randomised controlled trials are available, no definite answer can be provided regarding the optimal strategy for staging, restaging and treatment of the different subsets of stage IIIA-N2 disease. Every patient with locally advanced NSCLC should be discussed within a multidisciplinary tumour board including radiation oncologists and thoracic surgeons who have a large experience with major lung resections. The best available diagnostic and treatment strategies should be discussed with the patient. Salvage surgery should be reserved for those centres having a large experience in thoracic surgery where a dedicated team is available as management of these patients requires multidisciplinary cooperation preoperatively, intraoperatively and postoperatively. References 1. Eberhardt WE, De Ruysscher D, Weder W, Le Péchoux C, De Leyn P, Hoffmann H et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol 2015; 26:1573-88. 2. Eberhardt WE, Pöttgen C, Gauler TC, Friedel G, Veit S, Heinrich V et al. Phase III study of surgery versus definitive concurrent chemoradiotherapy boost in patients with resectable stage IIIA-N2 and selected IIIB non-small-cell lung cancer after induction chemotherapy and concurrent chemoradiotherapy (ESPATUE). J Clin Oncol 2015; 33:4194-201. 3. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg 2014; 45:787-98. 4. Van Schil P. Stage IIIA-N2 non-small-cell lung cancer: from “surprise” involvement to surgical nightmare. Eur J Cardiothorac Surg 2016; 49:1613-4. 5. Le Péchoux C, Dunant A, Faivre-Finn C, Thomas PA, Pourel N, Lerouge D et al. Postoperative radiotherapy for pathologic N2 non-small cell lung cancer treated with adjuvant chemotherapy: need for randomized evidence. J Clin Oncol 2015; 33:2930-1. 6. Pless M, Stupp R, Ris HB, Stahel RA, Weder W, Thierstein S et al. Induction chemo-radiotherapy in stage IIIA/N2 non-small cell lung cancer: a phase 3 randomised trial. Lancet 2015; 386(9998):1049-56. 7. McElnay PJ, Choong A, Jordan E, Song F, Lim E. Outcome of surgery versus radiotherapy after induction treatment in patients with N2 disease: systematic review and meta-analysis of randomised trials. Thorax 2015; 70:764-8. 8. Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA et al. Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3[rd] ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143 (5 Suppl): e314-30S. 9. Van Schil P. Salvage surgery after stereotactic radiotherapy: a new challenge for thoracic surgeons. J Thorac Oncol 2010; 5:1881-2. 10. Schreiner W, Dudek W, Sirbu H. Is salvage surgery for recurrent non-small-cell lung cancer after definitive non-operative therapy associated with reasonable survival? Interact Cardiovasc Thorac Surg 2015; 21: 682-4.

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    P1.03 - Poster Session with Presenters Present (ID 455)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.03-028 - Wolf in Sheep's Clothing - Primary Lung Cancer Mimicking Benign Diseases (ID 3937)

      14:30 - 15:45  |  Author(s): P.E. Van Schil

      • Abstract
      • Slides

      Background:
      Lung cancer is the biggest cancer killer and typically presents as mass or nodule, round or oval in shape. Recognition and diagnosis of these typical cases is often straightforward, whereas diagnosis of uncommon manifestations of primary lung cancer certainly is far more challenging. The aim of this pictorial essay is to illustrate the Computed Tomography (CT) and histopathology findings of uncommon manifestations of primary lung cancer with focus on these entities that mimic benign diseases.

      Methods:
      Cases presented were collected during the Multidisciplinary Thoracic Oncology Tumor Board between January 2014 and May 2016 and have histopathologic proof.

      Results:
      Lung cancer can mimic a variety of benign diseases, including infection, granulomatous disease, lung abscess, postinfectious scarring, mediastinal mass, emphysema, atelectasis and pleural disease. Previous history, clinical and biochemical parameters are certainly helpful and necessary in the assessment of these cases, but often aspecific and inconclusive. Whereas 18FDG-PET is the cornerstone in diagnosis and staging of lung cancer, it’s role in these uncommon manifestations is less straightforward since benign diseases, such as granulomatous and infectious diseases may also present with increased FDG-uptake. Chest CT is the imaging modality of choice and plays a central role in these cases. ‘Irregular air bronchogram sign’ in pneumonia-like lung cancer, ‘drowned lung sign’ in obstructive atelectasis and cortical bone erosion in lung cancer mimicking pleural disease are important signs that point to a malignant etiology. The stippled and eccentric morphology of calcifications in apical lesions aids in differentiating these lesions from postinfectious scarring. Mucinous tumours can mimic a pulmonary abscess and small cell lung cancer can typically present as mediastinal mass without parenchymal abnormalities. Lung cancer presenting with a miliary pattern or cavitating nodules can mimic granulomatous disease. Lung cancer presenting with cystic airspaces and ‘emphysema-like’ morphology is an uncommon entity in which early recognition is crucial since these tumors have an aggressive nature. Key imaging findings and tips and tricks for recognizing these uncommon faces of primary lung cancer will be discussed and illustrated.

      Conclusion:
      Primary lung cancer can mimic a wide variety of benign entities. Knowledge of these uncommon and atypical manifestations is crucial to avoid delay in diagnosis and treatment. A multidisciplinary approach in these cases is mandatory.

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