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F. Detterbeck
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GR01 - Surgery and the New Stage IIIA (ID 16)
- Event: WCLC 2013
- Type: Grand Round Session
- Track: Surgery
- Presentations: 4
- Moderators:F. Detterbeck, J. Mitchell
- Coordinates: 10/29/2013, 14:00 - 15:30, Parkside Ballroom A, Level 1
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GR01.1 - Surgery for N2 Disease: Where To and When To Now? (ID 446)
14:05 - 14:25 | Author(s): M. Tsuboi
- Abstract
- Presentation
Abstract not provided
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GR01.2 - Where Does T3 Eend and T4 Begin? (ID 447)
14:25 - 14:45 | Author(s): V. Rusch
- Abstract
- Presentation
Abstract not provided
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GR01.3 - Role of Neoadjuvant and Adjuvant Therapies (ID 448)
14:45 - 15:05 | Author(s): S. Watanabe
- Abstract
- Presentation
Abstract
1. Introduction Lung cancer has remained to be the leading cause of cancer-related death in many countries. Most patients are diagnosed at an advanced stage, stage III or IV. A way to improve surgical outcome would be the administration of chemotherapy before or after the surgical procedure. 2. Neoadjuvant therapy The preoperative induction therapy offers several benefits: (1) an increased percentage of patients completing the planned dose of chemotherapy, (2) the probability to treat micrometastatic tumor dissemination preoperatively, (3) the ability to assess response to the chemotherapy as a prognostic indicator, and (4) the probability to increase resectability by the tumor regression. 2.1. Induction chemotherapy Numbers of phase II trial using induction chemotherapy can be found in the previous literatures. Phase III neoadjuvant trial results including stage IIIA disease are summarized in Table1. Two studies reported by Roth (1994) and Rosell (1994) suggested that induction therapy followed by surgery could lead to improved outcomes, however, recent large scale studies did not show the improvement of survival in stage IIIA patients received neoadjuvant chemotherapy. 2.2. Induction chemotherapy with third-generation agents Results of previous studies, all of them are phase II study, evaluating the efficacy of induction chemotherapy with third-generation agents are shown in the table 2. These trials showed the feasibility and potential benefit of induction chemotherapy with combination or cisplatin and third-generation agents for stage III patients. Since the data of phase III trial with large sample size are lacking, the adequate regimen of induction chemotherapy has yet to be defined. 2.3. Induction chemotherapy or induction chemoradiotherapy? Whether induction radiotherapy adds benefit when surgery is planned is an important clinical question, because the addition of each modality increase the possibility of morbidity and mortality of treatment. To investigate the benefit of neoadjuvant radiation therapy, Shah (2012) conducted systematic review and meta-analysis. None of the studies demonstrated a survival benefit to adding induction radiotherapy to induction chemotherapy versus induction chemotherapy alone. The meta-analysis performed on randomized studies demonstrated no benefit in survival from adding radiation (HR: 0.93; p=0.81), nor did the meta-analysis performed on retrospective studies (HR: 0.77; p=0.24). The most promising use of induction chemoradiotherapy is to treat the superior sulcus tumor (SST) where preoperative local tumor regression is a key to achieving complete resection. Rush (2007) reported the results of SWOG 9416 (Intergroup 0160) phase II trial, which tested the feasibility of induction chemoradiotherapy for SST, on the basis of improved outcomes in other subsets of stage III NSCLC. Pathologic complete response (CR) or minimal microscopic disease was seen in 61 (56%) resection specimens. Five-year survival was 44% for all patients and 54% after complete resection, with no difference between T3 and T4 tumors. Kunitoh (2008) reported the similar results of Japan Clinical Oncology Group (JCOG) phase II trial (JCOG 9806), which was conducted for testing the feasibility of induction chemoradiotherapy for NSCLC-SST patients. There were 12 patients with pathologic CR. The disease-free and overall survival rates at 3 years were 49% and 61%, respectively; at 5 years, they were 45% and 56%, respectively. They concluded that the trimodality approach was safe and effective for the treatment of patients with SST 3. Adjuvant therapy 3.1. Adjuvant chemotherapy The NSCLC Collaborative Group (1995) reported a meta-analysis of 14 clinical trials addressing the role of adjuvant chemotherapy for resected NSCLC. There was no statistically significant survival benefit in group of patients received adjuvant chemotherapy, but a trend toward better survival prompted further studies. Subsequently, the Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis based on individual patient data collected from the 5 largest trials (4,584 patients) of cisplatin-based adjuvant chemotherapy in completely resected patients with NSCLC was performed. This analysis also showed a significant survival benefit with adjuvant chemotherapy, with an overall hazard ratio (HR) of 0.89, translating into a 5-year absolute survival benefit of 5.4%. Then in 2010, the NSCLC Meta-analyses Collaborative Group reported a meta-analysis of 34 clinical trials with 8,447 patients (3,323 deaths) addressing the benefit of adjuvant chemotherapy for resected NSCLC. Among those, the overall hazard ratio to survival in patients received cisplatinum-based adjuvant chemotherapy by stage suggests absolute improvements in 5-year survival of 5% for stage III disease (from 30% to 35%). 3.2. Adjuvant radiotherapy In 1988, postoprative radiotherapy (PORT) Meta-analysis Trialists Group collected individual data on 2,128 patients from nine available randomized trials of PORT versus surgery alone. They reported a 21% relative increase in the risk of death, which was equivalent to an absolute detriment of 7% at 2 years, with PORT reducing overall survival from 55% to 48% after resection. Subgroup analysis suggested that the adverse effect on overall survival was most notable for patients with stage I/II (N0-N1) tumors, whereas there was no clear evidence of either adverse effect or benefit for stage III disease. The results of the PORT meta-analysis, however, are probably not applicable to current therapy because of recent major improvements in radiation treatment planning and delivery. 4. Neoadjuvant or adjuvant chemotherapy? Which is the better treatment, induction or adjuvant chemotherapy? Some concern has also arisen regarding adjuvant chemotherapy compliance, with most trials using cisplatin doublets reporting delivery of only 60% of planned treatment. Induction chemotherapy seems better tolerated, more than 80% of the patients received the full planned treatment at the difference of adjuvant chemotherapy. In the LACE meta-analysis, 33% of patients in the chemotherapy arm did not start or finish the planned chemotherapy regimen, reflecting the difficulty of adjuvant chemotherapy administering such taxing therapies to a postoperative population. 6. Conclusions Although definitive chemoradiation remains a standard of care for stage IIIA NSCLC, alternative approaches such as induction chemotherapy and surgery for a selective group of patients can be considered. When surgical resection after induction therapy can be performed with low risk and a good chance of complete resection, it might provide an optimal outcome. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection. Figure 1Figure 2Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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GR01.4 - Multiple Primaries, Satellites or Intrapulmonary Metastases? (ID 449)
15:05 - 15:25 | Author(s): R. Calhoun
- Abstract
- Presentation
Abstract not provided
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MO03 - Thymic Malignancies (ID 123)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 11
- Moderators:F. Detterbeck, M. Okumura
- Coordinates: 10/28/2013, 10:30 - 12:00, Bayside Gallery B, Level 1
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MO03.01 - Outcome of surgical treatment for thymic epithelial tumors based on the nationwide retrospective database of 3033 patients in Japan (ID 2284)
10:30 - 10:35 | Author(s): M. Okumura, Y. Fujii, I. Yoshino, H. Asamura, K. Yoshida, H. Date, K. Nagai, K. Yokoi, J. Nakajima, S. Miyoshi, K. Kondo
- Abstract
- Presentation
Background
Thymic epithelial tumor, consisting of thymoma, thymic carcinoma and thymic neuroendocrine carcinoma, is a relatively rare neoplasm, and there is not a satisfying consensus in the treatment strategy. Because of lack of TNM staging system and global consensus on pathological classification, global research in these research has been difficult. To participate in movement of establishing the global database, Japanese Association for research of the Thymus (JART) conducted the project of Japanese nation-wide database in 2012.Methods
Patients undergoing surgical treatment during 20 years between 1991 and 2010 in Japan were collected from 32 institutes. 3182 patients were first enrolled, but after exclusion of cases with insufficient information, 3033 cases remained for analysis finally.Results
1435 patients (44%) were male, and 1595 were female (not identified in 3 patients). The age at operation was 13 to 88 years (mean 57 years old). Pathological diagnosis was thymoma in 2505 patients (Type A: 203, Type AB: 710, Type B1: 599, Type B2: 669, Type B3: 329), thymic carcinoma in 381 patients (Squamous cell carcinoma: 223, neuroendocrine carcinomas 66), and unclassified or unknown in 147 patients. According to Masaoka staging system, 1063 patients were in stage I, 1084 were in stage II, 477 in stage III, 197 in stage IVA, 57 in stage IVB (undetermined in 155 patients). Complete resection was achieved in 2753 patients (92%), subtotal resection (mass reduction of more than 80%) in 157 patients (5%), partial resection including biopsy in 86 patients (unknown in 37 patients). 249 patients were alive with tumor. 316 patients were dead during the observation period, and 161 patients died from tumor. Among 2557 patients who underwent complete resection (R0), 269 patients (10.5%) had tumor recurrence. In the patients who underwent complete or subtotal resection, 10-year overall survival rate was 89% in thymoma, 56% in squamous cell carcinoma, 30% in non-squamous thymic carcinoma, 72% in well-differentiated neuroendocrine carcinoma and 29% in poorly-differentiated neuroendocrine carcinoma. According to Masaoka stage, 10-year overall survival rate was 94% in stage I, 93% in stage II, 74% in stage III, 59% in stage IVA and 44% in stage IVB. In thymoma patients who underwent complete resection, recurrence-free survival rate at 10 years was 96% in type A, 99% in type AB, 92% in type B1, 80% in type B2, 72% in type B3. By Cox’ proportional hazard model, involvement of the mediastinal pleura (p=0.01), involvement of the lung (p=0.01), pleural dissemination (p=0.0009), distant metastasis (p=0.01) and WHO histological subtype (p<0.0001) were found to be independent factors for tumor recurrence after complete resection, while nodal metastasis, intrapericardial dissemination, involvement of pericardium, pulmonary artery, SVC, brachiocephalic vein, aorta, or brachiocephalic artery were not.Conclusion
Japanese nation-wide database revealed the oncological difference among thymoma, thymic carcinoma and thymic neuroendocrine carcinoma. In thymoma, involvement of pleura and lung, pleural dissemination, distant metastasis and WHO histological classification were significant factors of tumor recurrence. These results are supposed to contribute to clinical practice for tumor treatment as well as establishment of global TNM classification.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.02 - Surgical Outcome of Patients with Stage III Thymoma in the Japanese Nationwide Database (ID 2842)
10:35 - 10:40 | Author(s): Y. Yamada, I. Yoshino, Y. Fujii, H. Asamura, K. Yoshida, H. Date, K. Nagai, K. Yokoi, J. Nakajima, S. Miyoshi, K. Kondo, M. Okumura
- Abstract
- Presentation
Background
Stage III thymoma has a variety characteristics in terms of involved organs, complex surgery and multimodal strategy, and a careful consideration is required in choices of treatments. Recently the Japanese Association for Research on the Thymus (JART) conducted a nationwide large cohort analysis for thymic epithelial tumors. The aim of this study is to clarify clinical characteristics and therapeutic outcome of patients who underwent surgical resection for stage III thymoma using this database.Methods
Clinical data of 3,033 thymic epithelial tumor patients of 1991 to 2010 were collected rom 32 Japanese institutes. Medical information registered included patients’ characteristics, types of surgery, pathological diagnosis, perioperative therapy, and clinical outcomes were registered. In this study, stage III thymoma patients who underwent surgery were extracted from the database, and retrospectively analyzed for clinical characteristics and surgical outcome.Results
A total of 340 records of patients were analyzed in this study, which comprised 186 males (54.7%) and 153 females (45.0%), 83 (24.4%) with myasthenia gravis, 42 (12.4%) with induction chemotherapy, 18 (5.3%) with preoperative radiotherapy, and 29 (8.5%) with adjuvant chemotherapies. WHO histologic types comprised 16 A (4.7%), 40 AB (11.8%), 47 B1 (13.8%), 118 B2 (34.7%) and 97 B3 (28.5%). Involved organs were lung in 209 (61.4%), pericardium in 167 (49.1%), chest wall in 7 (2.1%), phrenic nerve in 88 (25.9%) and great vessels in 134 (39.4%). Completeness of resection was R0 in 268 (78.8%), R1 in 35 (10.3%) and R2 in 20 (5.9%). Complications were observed in 85 (25.0%) including arterial fibrillation, phrenic nerve palsy, bleeding and crisis of myasthenia gravis, and 30-day mortality rate was 1.8% (6 cases). Tumor recurrence was experienced in 96 (28.2%), and 39 (11.5%) died during the observation. Overall and disease-free 10-year survival rates were 81.0% and 56.7%, respectively. Involved organs except for chest wall, completeness of resection or myasthenia gravis did not affect the survivals. Number of involved organs (1 vs. >2) and tumor length (<7cm vs. >7cm) affected disease-free survival but not overall survival. Among factors suggested to affect overall survival by univariate analyses such as male, surgical complication, WHO histologic type B1-3, chest wall invasion, induction treatments, and recurrence, independent adverse predictors were revealed by a multivariate analysis to be male (p=0.031, HR=2.47), induction chemotherapy (p=0.034, HR=2.39), postoperative complication (p=0.018, HR=2.41) and recurrence of disease (p=0.041, HR=2.15). Of 96 patients with recurrence, 47 patients who underwent salvage resection showed better prognosis than 49 patients who did not (p=0.009).Conclusion
This nationwide registry study exhibited favorable surgical outcome in Japanese patients with stage III thymoma. Effectiveness of multimodal treatments need to be further investigated in prospective controlled trials.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.03 - RYTHMIC: a nationwide network for thymic malignancies in France (ID 2631)
10:40 - 10:45 | Author(s): N. Girard, E. Pichon, P. Thomas, H. Léna, E. Dansin, G. Massard, G. Zalcman, J. Mazières, L. Thiberville, V. Westeel, P. Fournel, C. Clément-Duchêne, X. Quantin, J. Bennouna, T. Molina, B. Besse
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- Presentation
Background
RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a nationwide network for thymic malignancies, which was appointed in 2012 by the French National Cancer Institute, as part of its rare cancer program. The objectives of the network include a territorial coverage by regional expert centers, the dissemination of highest standards for the diagnostic and therapeutic management of patients, and the promotion of collaborative research. Registration in RYTHMIC of all patients diagnosed with thymic malignancy is recommended as part of good clinical practice for oncologists.Methods
Starting January 2012, the management of all patients diagnosed with thymic malignancy in France has been discussed on a real-time basis at a reference national multidisciplinary tumor board (MTB), which is organized twice a month using a web-based conferencing system. Decision-making is based on consensual recommendations, that were originally established using available evidence, and are updated and approved each year by all members of the network. A prospective database of all patients is hosted by the French Thoracic Cancer Intergroup. We report the characteristics and treatment modalities of patients included during the first year.Results
From January to December 2012, 257 patients were enrolled in RYTHMIC. There were 126 (49%) men and 131 (51%) women; mean age at diagnosis was 54.5 years. Among 214 cases, histology was thymoma for 146 (56%) patients (11 (5%) type A, 28 (13%) type AB, 22 (10%) type B1, 35 (16%) type B2, 24 (11%) type B3, 26 (12%) mixed type), and thymic carcinoma for 33 (15%) patients, 8 of which were neuroendocrine carcinomas; other histologies were diagnosed for 35 (16%) patients. Among 144 cases, Masaoka-Koga stage was I, IIA, IIB, III, IVA, and IVB in 34 (24%), 19 (13%), 20 (14%), 22 (15%), 35 (24%), and 14 (10%) patients, respectively. 44 (17%) patients presented with autoimmune disorder, consisting of myasthenia gravis in 28 cases. Surgery was performed for 166 patients, mostly using a median sternotomy approach (52% of cases). Postoperative radiotherapy was delivered to 42 patients; 71 patients received perioperative chemotherapy. Exclusive chemotherapy/radiotherapy was administered to 20 and 4 patients, respectively. Mature data will be presented at the meeting.Conclusion
This first analysis of the RYTHMIC prospective cohort demonstrates the feasibility of a national MTB for thymic malignancies, that, besides ensuring all patients an equal access to highly specialized treatment, provides with a comprehensive tool to monitor dedicated actions to improve the management of patients in the future, increase the quality-of-care, and screen patients for future translational research and clinical trials. Supported by Institut National du CancerOnly Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.04 - Analysis of lymphatic metastases of thymic epithelial tumors on Japanese database (ID 3196)
10:45 - 10:50 | Author(s): Y. Nakagawa, K. Kondo, J. Nakajima, M. Okumura, I. Yoshino, Y. Fujii, H. Asamura, K. Yoshida, H. Date, K. Nagai, K. Yokoi, S. Miyoshi, S. Sakiyama, A. Tangoku
- Abstract
- Presentation
Background
Thymic epithelial tumors sometimes metastasize to lymph nodes (LNs). The frequency of lymph node metastasis, the pattern of node metastasis and the relationship between prognosis and node metastasis are still unclear.Methods
We registered patients with thymic epithelial tumors who had undergone resection between 1991 and 2010 from 29 institutes in Japan by the Japanese Association for Research on the Thymus (JART). We investigated the collected data according to the site of lymphatic metastasis. Yamakawa-Masaoka's paper (Cancer 1991;68:1984–7.) tentatively classified the N factor to 3 groups: metastasis to anterior mediastinal lymph nodes around the thymus were defined as N1, metastasis to intrathoracic lymph nodes other than anterior mediastinal lymph nodes as N2, and metastasis to extrathoracic lymph nodes as N3.Results
The rate of lymphatic metastasis in thymoma was 1.75% (44 cases of 2508). Most of metastatic nodes were located in anterior mediastinal lymph nodes (N1, 78%). There is a significant difference of overall survival between thymomas with LN metastasis and those without LN metastasis (p<0.0001, 10-year survival: 89.8% vs 63.6%). Thymomas with N1 metastasis showed a good prognosis than those with other node metastasis, although there is no significant relationship (5-year survival: 64.4% vs 52.5%). The rate of lymphatic metastasis in thymic carcinoma including thymic carcinoid was 22% (84 cases of 380). Most of metastatic nodes were located in anterior mediastinal lymph nodes (N1, 69%). There is a significant difference of overall survival between thymic carcinomas with LN metastasis and those without LN metastasis (p<0.0001, 10-year survival: 59.5% vs 18.4%). Thymic carcimomas with N1 metastasis showed good prognosis than those with other node metastases, although there was no significant relationship (5-year survival: 55.5% vs 27.5%).Conclusion
The rate of lymphatic metastasis in thymoma and thymic carcinoma was 1.75% and 22%, respectively. Both tumors frequently metastasized to the anterior mediastinal nodes. There was a significant difference of overall survival between tumors with LN metastasis and without LN metastasis in both tumors. And both tumors with N1 metastasis showed good prognoses than those with other node metastases, although there was no significant relationship. We think that it may be reasonable to consider the anterior mediastinal lymph node group (N1) to be a primary lymph node of thymic epithelial tumor.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.05 - Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome. (ID 2020)
10:50 - 10:55 | Author(s): R. Berardi, A. Brunelli, S. Pagliaretta, V. Paolucci, M. Refai, G. Goteri, C. Pompili, G. Marcantognini, F. Morgese, Z. Ballatore, A. Savini, M. De Lisa, M. Caramanti, M. Santoni, P. Mazzanti, A. Onofri, A. Sabbatini, S. Cascinu
- Abstract
- Presentation
Background
Thymomas are uncommon tumors of thymic epithelial cells. Thymomas display significant heterogeneity from morphologic point of view, clinical behaviour, expression of immunohistochemical markers and molecular profiling. Improving our understanding of the molecular biology of thymic malignancies represents a key challenge in the treatment of these rare tumors.Methods
The genomic DNA of 57 consecutive patients (31 females and 26 males; 43 thymomas and 14 thymic carcinomas) submitted to total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes: Hypoxia Inducible Factor-1 alpha (HIF1a: rs2057482T>C, rs1951795A>C, rs2301113C>A, rs10873142C>T, rs11158358G>C, rs12434438G>A, rs11549465C>T, rs11549467G>A), Vascular Endothelial Growth Factor-A (VEGF-A: rs2010963G>C, rs699947A>C), VEGF Receptor 2 (VEGFR-2: rs2305948C>T, rs1870377T>A), VEGFR-3 (rs307826T>C, rs307821C>A), Platelet-Derived Growth Factor-A (PDGFR-A: rs35597368C>T) and Excision Repair Cross-Complementing 1 (ERCC1: rs11615A>G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays.Results
The allele frequency of PDGFR-A rs35597368 T (95.24%) was significantly higher than general population (86%, p=0.012), while the frequency of alleles HIF1-A rs2057482C (76.98%), rs1951795C (68.25%), rs2301113A (68.55%), rs10873142T (68.85%), rs11158358C (74.6%), rs12434438A (65.87%), rs11549465C (83.33%) were significantly lower than those of the control group (90%, 87%, 82%, 87%, 86%, 84%, 92%, respectively, p<0.01). VEGFR-3 rs307821C was significantly higher in thymomas vs. thymic carcinomas (79.5% vs 72%, p=0.0371). The following factors were significantly correlated with a better overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-A rs35597368T/C, HIF1a rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p<0.05).Conclusion
To the best of our knowledge this is the largest monocentric study analyzing the angiogenetic variants in thymic tumors representing a further asset in the definition of high-risk patients after curative resection. The selection tool deriving from this analysis may allow an optimal use of innovative treatment strategies including targeted agents such as sunitinib, sorafenib or pazopanib.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.06 - DISCUSSANT (ID 3974)
10:55 - 11:10 | Author(s): J. Huang
- Abstract
- Presentation
Abstract not provided
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MO03.07 - Clinical activity of sunitinib in patients with thymic carcinoma (ID 3114)
11:10 - 11:15 | Author(s): A. Thomas, A. Rajan, A. Berman, B. Scepura, C. Brzezniak, C.A. Carter, U. Guha, Y. Wang, E. Szabo, P.J. Loehrer, G. Giaccone
- Abstract
- Presentation
Background
There are no standard treatments for patients with advanced thymic epithelial tumors (TET) in whom chemotherapy has failed. A subset of TETs over-express and harbor activating mutations of KIT. Moreover, expression of angiogenic markers correlate with invasiveness of TETs. This two-center phase II study was conducted to evaluate efficacy of sunitinib, a multi-targeted tyrosine kinase inhibitor that blocks angiogenic and other growth factors in TETs.Methods
Patients with TET who had progressive disease following at least one platinum-based chemotherapy were enrolled. Sunitinib was administered orally at 50 mg once daily in 6 week cycles for 4 weeks followed by 2 weeks off until disease progression. Tumor response was assessed by computed tomography scans every 6 weeks. KIT mutations were assessed in archival tissue. Primary end-point was objective response rate in parallel cohorts (thymoma, thymic carcinoma).Results
Between May 2012 and June 2013, 22 patients with thymic carcinoma [median age 58 (40-81); males 59%] and 16 with thymoma [median age 54 (31-74); males 44%] enrolled. Median of 4 (range, 1-7) and 3 (range, 1-8) cycles were administered in patients with thymic carcinoma and thymoma respectively. Among 19 evaluable patients with thymic carcinoma, there were three partial responses (16%) and 10 minor responses (50%) (Figure). Thirteen patients had stable disease (68%) and three progressive disease (16%). After median follow up of 7.8 months, the median progression-free survival was 6.2 months and 6-month survival probability 85%. In contrast, only one out of 16 patients with thymoma had a partial response (6%). Twelve patients had stable disease (75%) and three progressive disease (19%). After median follow up of 6.4 months, median progression-free survival was 5.5 months and 6-month survival probability 90.9%. Grade 3 or 4 sunitinib-related adverse events which occurred in >10% of patients included neutropenia (18%), thrombocytopenia (23%), leucopenia (18%), lymphopenia (45%), fatigue (36%), mucositis (32%) and hypertension (18%). Three patients (14%) has symptomatic decline in left ventricular ejection fraction which improved with medical management and discontinuation of sunitinib. KIT mutations were absent in tumors of 20 patients who underwent mutational analysis.Figure 1Conclusion
In this phase II trial, sunitinib demonstrated anti-tumor activity unprecedented for a targeted agent in previously treated patients with thymic carcinoma. Activity was modest in thymoma. These results are intriguing as response rates of thymic carcinomas are usually lower than that for thymomas. KIT mutations did not predict responses. Ongoing exploratory analyses are evaluating biologic determinants of activity and mechanisms of resistance.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.08 - Increased Galectin-1 Expression in a Thymic Epithelial Tumor Tissue Microarray (TMA) and Galectin-1 Knockdown Studies in a Thymoma Cell Line (ID 1238)
11:15 - 11:20 | Author(s): J.W. Riess, P. Kuo, C. Kong, R. West, H.A. Wakelee, Q. Le
- Abstract
- Presentation
Background
Thymoma is a rare malignancy with a paucity of data on biology. Thymic epithelial tumors are often admixed with developing T-lymphocytes in the microenvironment. Galectin-1 (gal-1) is a beta-galactosidase binding protein involved in T-cell development via thymic stromal and thymocyte interaction as well as thymocyte development through negative selection. Gal-1 also induces apoptosis of effector T-lymphocytes, promotes angiogenesis, and is a poor prognostic indicator when overexpressed in several tumor types. To our knowledge expression of gal-1 has not been examined in thymic epithelial tumors.Methods
A TMA was constructed from 68 patients with thymic malignancies and 8 benign thymic controls at Stanford University School of Medicine (Stanford, CA). Immunohistochemical stains for galectin-1 (1:200 dilution; citrate pre-treatment; mouse monoclonal; Novocastra) were performed on 4 µM-thick TMA sections. Galectin-1 cytoplasmic staining of the epithelial cell component was scored as negative (0), focal positive (1+), or strong positive (2+) by a Stanford pathologist, who was blinded to the clinical data. Gal-1 expression was averaged for each patient sample. Statistical analysis was performed using SAS Enterprise Guide v5.0 (Cary, NC). Non-parametric statistical analyses were used to compare average patient gal-1 expression between thymic tumors and benign thymic controls. Stable gal-1 knockdown was achieved in IU-TAB1, a human thymoma WHO type AB cell line, using the pLKo.1 vector with gal-1 shRNA (Open Biosystems). Lentivirus was produced using the Trans-Lentiviral Packaging System (Thermo Scientific). In vitro proliferation cell counts were performed by hemocytometer. After hypoxia exposure (0.5% O~2~), apoptotic cells were labeled using the APO-Direct kit and quantified by flow cytometry (BD Biosciences).Results
Demographics for 68 patients: M:F (53%/47%), Mean age at diagnosis: 55 years, WHO Histology: A (10%), B (57%), AB (24%), C (4%), unclassified (4%), Pathologic Maseoka Stage: I (46%), IIa (18%), IIb (4%), III (18%), IVa (9%) IVb (6%). Gal-1 expression was increased among thymic tumor tissue compared to unpaired controls (mean avg gal-1 expression 1.5 vs. 0.125, p=0.0012, Kruskal-Wallis test). Logistic regression of tumor vs. control thymus by gal-1 generated a C-statistic of 0.845. A significant increase in gal-1 expression was noted across all WHO thymoma subtypes except thymic carcinoma (type C) (p < 0.05, non-parametric ANOVA with post-hoc ranked Dunnett’s t-test). Among 11 thymic tumors analyzed with paired adjacent resected benign thymus tissue from the same patient, a significant increase was noted in gal-1 expression among tumor compared with adjacent resected normal benign thymus (mean avg gal-1 1.82 vs. 0.35, p=0.004, sign-rank test). In vitro, gal-1 knockdown did not affect IU-TAB1 proliferation. Preliminary results showed gal-1 knockdown increased apoptosis under hypoxia compared to scramble control.Conclusion
Gal1 expression was increased among thymoma compared with benign thymus controls and paired adjacent resected benign thymus. A robust C-statistic of 0.845 indicates that gal-1 expression may discriminate tumor from benign thymus. Increased gal-1 expression was conserved across WHO histologic subtype except for thymic carcinoma—whose analysis was limited due to small sample size. Gal-1 knockdown might increase apoptosis under hypoxia. We are continuing to investigate the biologic and clinical significance of increased gal-1 expression in thymoma.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.09 - Detection of Human Polyomavirus 7 in thymomas (ID 1829)
11:20 - 11:25 | Author(s): M. Keijzers, A. Dingemans, D. Rennspies, S. Pujari, M.A. Abdul Hamid, M. Hochstenbag, E.M. Speel, A. Haugg, C. Buck, M. De Baets, A. Zur Hausen
- Abstract
- Presentation
Background
Thymomic pathologies are associated with the autoimmune disease myasthenia gravis (MG). The thymomagenesis have been studied extensively but the etiology of human thymoma remains poorly understood. Based on the consistent finding that murine polyomavirus induces thymomas in mice we tested the presence of Human Polyomavirus 7 (HPyV7) in human thymic epithelial tumors.Methods
We applied HPyV7 DNA Fluorescence in situ hybridization (FISH), DNA PCR and immunohistochemistry (IHC) in 37 thymomas (19 female, 18 male; mean age 58.3 years; range 34 – 82 years). Of these, 26 were previously diagnosed with MG. In addition, 2 thymic carcinomas, 20 follicular hyperplasia and 20 fetal thymus tissues were tested for HPyV7.Results
HPyV7 FISH revealed specific nuclear hybridization signals within the thymoma cells of 23 thymomas (62.2%). Fifteen thymomas revealed strong to very strong hybridization signals, whereas 8 revealed only weak positivity. With one exception the HPyV7 FISH data highly correlated with the HPyV7 DNA-PCR data. IHC showed the presence of HPyV7 on the translational level and immunohistochemical double stainings confirmed the presence of HPyV7 in the epithelial thymoma cellular compartment. One thymus carcinoma was HPyV7 positive the other negative. All fetal thymus tissues were tested HPyV7 negative. The follicular hyperplasia results are pending.Conclusion
We conclude that HPyV7 is frequently present in human thymic epithelial tumors and absent in fetal thymic tissues. No convincing association on HPyV7 and MG could be found. In as much HPyV7 is of relevance to human thymomagenesis remains to be established.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.10 - A multicenter prospective study of carboplatin and paclitaxel for advanced thymic carcinoma: West Japan Oncology Group 4207L (ID 987)
11:25 - 11:30 | Author(s): J. Shimizu, F. Hirai, T. Yamanaka, K. Taguchi, H. Daga, Y. Kogure, T. Kimura, K. Tanaka, Y. Iwamoto, A. Ono, H. Sasaki, J. Fukuoka, K. Nishiyama, K. Takeda, T. Seto, Y. Ichinose, K. Nakagawa, Y. Nakanishi
- Abstract
- Presentation
Background
Thymic carcinoma (TC) is a rare malignant tumor originated within the thymus gland and is associated with a poor prognosis, differing from thymoma which is the most common type of thymic malignant neoplasm. No results of clinical trials focusing on TC have been reported. This single-arm study evaluated carboplatin and paclitaxel (CbP) in previously untreated patients (pts) with advanced TC.Methods
Pts with Masaoka’s stage III to IVb TC, ECOG PS 0 to 1, and more than 20 years old were eligible. The study treatment consisted of carboplatin (AUC 6) and paclitaxel (200 mg/m2) every 3 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) by extramural assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. All pts were followed-up until 24 months (mo) after last enrollment. Based on the SWOG 2-stage design, the planned sample size of 40 pts was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05.Results
From May 2008 to November 2010, 40 pts were enrolled from 21 centers. Of 39 evaluable for analysis, the median age was 62 years (range, 36–84); 23/16 males/females; 3/10/26 with Masaoka’s stage III/IVa/IVb; 9/11/19 with squamous cell carcinoma/poorly differentiated neuroendocrine carcinoma/other types. The median number of cycles was 6. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval [CI], 21-53%; P = 0.031). The median PFS was 7.5 mo (6.2-12.3 mo) while OS did not reach the median value. The 1-year and 2-year survival rates were 85% (95% CI, 69-93%) and 71% (95% CI, 54-83%), respectively. Major adverse event was grade 3-4 neutropenia in 34 pts (87%). Two cases (5%) of grade 3 febrile neutropenia, neuropathy, and arthralgia were observed, respectively. There was no treatment-related death.Conclusion
CbP showed high efficacy in advanced TC. Our results established that CbP, one of the standard treatments for non-small cell lung cancer, also serves as a key chemotherapy regimen for TC.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO03.11 - DISCUSSANT (ID 3975)
11:30 - 11:45 | Author(s): H.A. Wakelee
- Abstract
- Presentation
Abstract not provided
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Author of
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MS16 - ESTS/IASLC Thymic Session (ID 33)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Thymoma & Other Thoracic Malignancies
- Presentations: 2
- Moderators:P. Goldstraw, E. Lim
- Coordinates: 10/30/2013, 10:30 - 12:00, Bayside Gallery A, Level 1
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MS16.2 - Towards a TNM-Based Prognostic Classification for Thymic Tumours (ID 531)
10:47 - 11:04 | Author(s): F. Detterbeck
- Abstract
- Presentation
Abstract
There are many impediments to achieving scientific progress in thymic malignancies, starting with the fact that these are relatively rare tumors. Another problem is the fact that there is no official stage classification system. At least 15 different systems have been proposed, all of which have been based on a limited number of patients, and none of which has been universally adopted with clear definitions that are consistently interpreted. This lack of a common basic language is a crucial fundamental building block for scientific advancement. The International Thymic Malignancies Interest Group (ITMIG) is an academic organization devoted to promoting the scientific advancement in thymic and other mediastinal malignancies. ITMIG has partnered with IASLC to develop proposals to the AJCC/UICC for the 8[th] edition of the stage classification system. This process began in 2010 and is now in full swing. ITMIG has pulled together an international database of approximately 9,000 patients. This involves 77 centers and 16 countries, with a notable major contribution from the Japanese Association for Research in the Thymus (JART). This data, together with an additional approximately 1,800 patients provided by the ESTS have been made available to CRAB, the statistical center for IASLC stage classification analyses. The Thymic Domain of the Staging and Prognostic Factors Committee (SPFC) is currently analyzing this data. The committee is considering multiple factors, starting with an analysis of the prognostic value of the Masaoka and Masaoka-Koga stage classification systems. Subcommittees of the thymic domain are also looking specifically at T, N, M factors, the impact of tumor size, invasion into particular structures and clinical stage. Internal validation will be performed, considering treatment factors, clinical stage, histologic subtypes, geographic regions and taking into account both survival and recurrence. Potentially useful factors will be compared to assess the relative impact, and to select the best factors to propose for use in the 8[th] edition stage classification system.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS16.3 - Surgery for Thymic Tumours: Outcomes from the ESTS Data Base (ID 532)
11:04 - 11:21 | Author(s): F. Detterbeck
- Abstract
- Presentation
Abstract
Introduction: Thymic tumors are rare malignancies and most of the current literature is composed of single-institutional series collecting small number of patients spanned over short time periods. The European Society of Thoracic Surgeons (ESTS) thymic working group developed a retrospective database among its members collecting patients with thymic tumors submitted to surgical resection between 1990 and 2010. Methods: A total of 2151 patients were collected from 35 Institutions, including 1798 thymomas, 191 thymic carcinomas (TC), and 41 Neuroendocrine Thymic Tumors (NETT)). 1709 patients (89%) received a complete resection. Myasthenia Gravis (MG) was present in 629 patients (35%). Different clinical-pathologic characteristics were analyzed for their impact on survival and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival (DFS) and the cumulative incidence of recurrence (CIR). Results: Ten-year OS and DFS rates were 73% and 70%. The risk of mortality increased with age and with the stage. It also increased in the presence of TC, NETT and incomplete resection. Ten-year CIR was 12%. Predictors of incomplete resection included male gender, tumor size, the absence of MG, non-thymoma categories (TC and NETT) and high-risk thymomas (B2-B3). The risk of recurrence increased with tumor size, increased stage and NETT. Finally, our analysis indicates that the overall effect of adjuvant therapy after complete resection on OS was significantly beneficial (p=0.05) using a propensity score. Conclusions: Masaoka stages III-IV, incomplete resection and non-thymoma histology showed a significant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved survival.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
