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M. Okumura



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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: 1
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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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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.02-026 - Individualized Adjuvant Chemotherapy for Resected Lung Cancer According to Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test (ID 3959)

      14:30 - 15:45  |  Author(s): M. Okumura

      • Abstract
      • Slides

      Background:
      The efficacy of adjuvant chemotherapy for locally advanced lung cancer cannot be assessed during the treatment, since there is no measurable lesion after surgical resection. We conducted a prospective clinical trial according to the results of drug sensitivity test with an aim to individualize adjuvant chemotherapy.

      Methods:
      Patients with resectable c-Stage IB-IIIA non-small cell lung cancer were registered between 2005 and 2010. Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) was performed on fresh surgical specimen. The clinical utility and prognostic outcome of adjuvant chemotherapy with carboplatin/paclitaxel in patients who showed chemo-sensitivity on CD-DST were evaluated. The primary endpoint was disease-free survival, and the secondary endpoints were overall survival and adverse effects during chemotherapy.

      Results:
      Among 92 registered patients, 87 (p-Stage IB in 54, IIA in 4, IIB in 10, IIIA in 19) were eligible and were included in the analysis. All patients were followed up for more than 5 years. The median age was 66 years old. The success rate of CD-DST was 87% and chemo-sensitivity to carboplatin and/or paclitaxel was observed in 75% of patients. Adjuvant chemotherapy was completed in 70% and the 5-year disease-free and overall survival rates were 68% and 82%, respectively. The 5-year disease-free and overall survival rates in Stage II–IIIA patients were 58% and 75%, respectively. As for the adverse effects during adjuvant chemotherapy, grade 4 neutropenia was found in 13%. Figure 1



      Conclusion:
      Chemo-sensitivity could be evaluated using CD-DST after lung cancer surgery. CD-DST might contribute to individualized adjuvant chemotherapy for locally advanced lung cancer.

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