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M. Masuda



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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P1.07-035 - Uncertain Resection due to incomplete intraoperative nodal assessment (ID 2321)

      09:30 - 16:30  |  Author(s): M. Masuda

      • Abstract

      Background
      The standard surgical approach for non-small-cell lung cancer is lobectomy with systematic hilar and mediastinal lymph node dissection. The purpose of lymph node dissection is considered to be improvement of prognosis and intraoperative staging. Although improvement of prognosis is controversial, it is clear that intraoperative nodal assessment is important for identifying N2 disease and making postoperative therapeutic decisions. For complete resection (CR), at least three mediastinal nodes including subcarinal nodes and three hilar/ intrapulmonary nodes had to be retrieved. Otherwise It is defined as uncertain resection(UR). The objective of this study is to clarify the difference of prognosis between CR and UR.

      Methods
      The medical records and the follow-up data of the patients operated for NSCLC(c-stage I to III) between January 2005 and December 2006 in Yokohama City University Hospital and 8 associate hospitals were analyzed retrospectively. Four hundred-eighty-four patients with NSCLC who underwent lung resections (lobectomy or pneumonectomy) with negative surgical margins were included in this study. Complete resection (CR) was performed in 198 patients. And in 286 patients, uncertain resection was done. We compared these 2 groups.

      Results
      There were no statistically difference between the both groups for age, gender, pathological stage( IA:CR n=69/UR n=153,IB 59/71,IIA 4/12,IIB 27/21,IIIA 36/24,IIIB 3/5), and histology (adenocarcinoma: CR n=122/UR n=185,squamous carcinoma:51/68,large cell carcinoma:15/14,others:14/20 respectively). Five-year disease-free-survival rate in the CR group was 58.1% compared with 63.3% in the UR group. Among patients with p-stage I, the 5-year disease-free-survival rate was significantly lower in UR group (78.1%) than in CR group (88.0%, p=0.027).

      Conclusion
      Uncertain resection might not be enough for accurate intraoprerative staging to determine pN0 status. However whether the accurate intraoperative staging leads to good prognosis was unclear.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-010 - surgical treatment and outcome of multiple primary lung cancers (ID 1153)

      09:30 - 16:30  |  Author(s): M. Masuda

      • Abstract

      Background
      Recently, multiple primary lung cancer is inreasing with progress of imaging diagnostic technology and improvement in treatment results. We assesed the selection of the type of pulmonary resection, operative morbidity, mortality and the outcome of our cases which enforced surgical treatment for multiple primary lung cancer.

      Methods
      Of 840 patients who underwent operation for primary lung cancer between January 2001 and May 2013.We consider 57(6.7%) to have a multiple primary lung cancer. We use the criteria of Martini and Melamed as a diagnosis of multiple primary lung cancer.

      Results
      The group comprised 27 men and 30 women. Median age was 66.7 years (48-80). It occured synchronous in 21 cases and metachronous in 36 cases. Cell type combination was adenocarcinoma-adenocarcinoma in 37 cases, adenocarcinoma-squamous cell carcinoma in 10 cases, squamous cell carcinoma-squamous cell carcinoma in 6 cases, adenocarcinoma-large cell carcinoma in 3 cases and large cell carcinoma-large cell carcinoma in 1 case. Operative procedures was lobectomy-lobectomy in 13 cases, lobectomy-segmentectomy in 12 cases, lobectomy-edge resectionin 19 cases, edge resection-edge resection in 5 cases and lobectomy/edge resection-radio therapy in 3 cases. Pathological stage for the first cancer was IA/IB/IIA/IIB/III = 35/14/4/0/4. The 5 year survival rate after first surgery was 81.7%, and second surgery was 72.2%.

      Conclusion
      With this result, we consider that surgical resection may prove beneficial in cases which postoperative good survival can be expected by the aggressive surgical approach, despite it is difficult to distinguish multiple primary lung cancers and metastatic cancers preoperatively.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 2
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      P2.18-019 - Clinicopathological features in non-small cell lung cancer patients with EGFR and KRAS mutations. (ID 2985)

      09:30 - 16:30  |  Author(s): M. Masuda

      • Abstract

      Background
      Some of molecular pathways have been shown to have prognostic impact in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations predict the effect of EGFR tyrosine kinase inhibitors. KRAS is also critical oncogene, and it has been reported that KRAS pathway might interact with EGFR. But, the role of KRAS in NSCLC is unclear. We investigated the relationship between EGFR and KRAS mutation status and clinicopathological features in NSCLC.

      Methods
      A total of 383 consecutive patients with NSCLC underwent complete resection from 2006 to 2008 were examined retrospectively. The expression of EGFR and KRAS were evaluated by tissue microarray.

      Results
      The mutations of EGFR and KRAS were detected in 181/383 (47.3%) and 32/383 (8.4%) patients, respectively. On analysis of EGFR mutations, female were 107/181 (59.1%) and 51/202 (25.2%), adenocarcinoma were 177/181 (97.8%) and 123/202 (60.9%), no vascular invasion were 147/181 (81.2%) and 110/202 (54.5%), and non-smoker were 99/181 (54.7%) and 41/202 (20.3%) patients in EGFR mutation and wild type patients, respectively. As a result, EGFR mutation was found more frequently in female, adenocarcinoma, no vascular invasion, and non-smoker. The number of patients with pathological T1a were 49/181 (27.0%) and 42/202 (20.8%), T1b were 63/181 (34.8%) and 41/202 (20.3%) in EGFR mutation and wild type patients, respectively. Moreover, average tumor diameter was smaller in patients with EGFR mutation (2.68 cm±0.92) than wild type (3.34cm±1.70) (P<0.001). There were no differences in clinicopathological characteristics between exon19 and 21 EGFR mutations. In contrast, there were no significant differences between KRAS mutation and gender, histopathological type, vascular invasion and.smoking. Although KRAS status was not correlated with pathological T factors, average tumor diameter was larger in patients with KRAS mutation (3.49 cm±2.00) than wild type (2.98 cm±1.35) (P<0.001).

      Conclusion
      Our results suggest that EGFR mutation may suppress vascular invasion, and tumor growth, on the other hand, KRAS mutation may correlate with activation of tumor growth.

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      P2.18-020 - Appropriateness Evaluation of Handling Method for the Small Lung Adenocarcinoma in the Frozen Section Diagnosis by Radiological-Pathological Correlation (ID 3007)

      09:30 - 16:30  |  Author(s): M. Masuda

      • Abstract

      Background
      The frozen section diagnosis is often performed in the sublobar resection of lung tumor. As no standard of preparation method for the frozen section is proposed, its methodology differs depending on institutions. In this study, we examine appropriateness of our preparation method for a resected specimen with a small adenocarcinoma by comparing between radiological and pathological tumor size.

      Methods
      We retrospectively reviewed the records of 59 resected lung specimens for the frozen section diagnoses (54 wedges and 5 segmentectomies) of lung adenocarcninomas from January to December 2008. After the specimen was well inflated with saline using injector, the pathologist cut it into segments with a width of 3-5mm and immersed them in saline. Taking the segment with maximum diameter of tumor as a sample, the pathological tumor sizes were measured (I) macroscopically by using metal straight ruler, (II) microscopically on the frozen section, and (III) microscopically on the permanent paraffin section. For obtaining the stereoscopic tumor size (Ⅱ and Ⅲ), we used a stereoscopic image analysis software, Leica Application Suite (Leica Microsystems; Tokyo, Japan). CT tumor size was measured by using 1-2mm thin-section CT (X-Vigor/Real or Aquillion, Toshiba Medical Systems, Tokyo, Japan). We obtained the tumor shadow disappearance rate (TDR) by comparing tumor size on the lung and mediastinal window image, to classify 59 cases into two groups according to TDR; TDR≧50% defined as the air-containing type (Group A, n=44) and TDR<50% as the solid-containing type (Group S, n=15). We also calculated the diremption rate (DR%) between the pathological and the CT tumor size (DR% = |CT tumor size - each pathological tumor size|/CT tumor size×100(%)) and compared Group A and Group S.

      Results
      Mean CT tumor size and its standard deviation(SD) were 18.36±5.23mm, and mean pathological tumor sizes and SD of Ⅰ, Ⅱ, and Ⅲ were 17.17±6.12, 14.29±3.66, and 14.23±4.38mm, respectively. Mean CT tumor size was statistically larger than that of Ⅱ and Ⅲ (p<0.001 using Paired t-test). All the three pathological tumor sizes were correlated to the CT tumor size by Pearson’s correlation analysis (correlation coefficient were 0.766, 0.700, and 0.682, respectively). DR% of Ⅱ and Ⅲ were significantly higher in Group A than Group S by Mann-Whitney U-test (Mean DR% of group A / S (p-values) of Ⅰ, Ⅱ, and Ⅲ were 17.0/13.8% (p=0.196), 25.8/19.3% (p=0.093), and 27.3/15.5% (p=0.032) , respectively).

      Conclusion
      There was a strong correlation between CT tumor size and each pathological tumor size, which shows that our preparation method of the specimen for the frozen section is appropriate to obtain sufficient information about the lung tumor. Furthermore, we found that the pathological tumor size is considerably underestimated by measuring tumor size on the frozen or permanent paraffin section, especially the tumor classified as “air-containing type” including adenocarcinoma with good prognosis. It is therefore important to inflate the lung specimen sufficiently and to transfer it to microscopical examination without tissue shrinking.

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-024 - The endo-finger technique for the localization of small pulmonary ground glass nodules under thoracoscopic surgery (ID 2089)

      09:30 - 16:30  |  Author(s): M. Masuda

      • Abstract

      Background
      Small pure ground glass nodules (GGNs) have sometimes been detected by high resolution computed tomography (CT). Pathologically, most of these pure GGNs are bronchioloalveolar carcinoma (BAC) or atypical adenomatous hyperplasia (AAH). In published papers, the thoracoscopic resection of the pure GGNs was reported to be difficult, because they cannot usually be palpated. Therefore, various marking techniques, such as those using a hook wire, colored collagen, barium, lipiodol and so on, have been described for the localization of pure GGNs. However, these techniques are associated with the development of several complications, such as pneumothorax, hemorrhage, and serious air embolism. Moreover, they requires a lot of time. In this study, we evaluated the localization of small pure GGNs in thoracoscopic surgery using the endo-finger technique.

      Methods
      Patients with peripheral pure GGNs that were 20 mm and less in diameter who planned to undergo resection in our institute were candidates for this study. Preoperatively, no marking technique was performed. Thoracoscopy was performed in the lateral position under single lung anesthesia. Thoracoports were placed near the GGNs based on the CT findings. One finger was inserted through the port into the pleural cavity to palpate the lung to localize the GGNs (the endo-finger technique). After the GGNs were detected, they were resected by endostaplers with adequate safety margin.

      Results
      Since January 2005, twenty patients with thirty-four GGNs were enrolled in this study. The size of the GGNs was 5 mm or less in eight lesions, 6 – 10 mm in 14 lesions, 11 – 15 mm in nine lesions and 16 – 20 mm in three lesions. The depth of the lesions from the visceral pleura ranged from 0 – 14 mm. The main reasons for the resection were a need for another ipsilateral simultaneous operation in six cases, the patients’ requests in five cases and enlargement of the GGNs during the follow-up period in three cases. All but one GGN could be detected using the endo-finger technique with two or three thoracoports, and were resected. Some of the GGNs adjacent to the visceral pleura were visualized by thoracoscopy as color changes in the visceral pleura. There was one conversion to thoracotomy in one patient who had a severe pleural adhesion due to a previous ipsilateral lobectomy of the lung. No complications occurred in association with this procedure. The pathological diagnoses of the GGNs were BAC in 23 nodules, AAH in nine, hyperplasia of the alveolar epithelium in one and an inflammatory lesion in one. The surgical margins of all of the resected specimens were pathologically negative.

      Conclusion
      The endo-finger technique is safe and useful for the localization and resection of peripheral GGNs during thoracoscopic surgery. We suggest that the preoperative marking to detect GGNs can be replaced by the endo-finger technique in some cases.

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    P3.24 - Poster Session 3 - Supportive Care (ID 160)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-042 - The use experience of crizotinib (XALKORI®) for postoperative recurrence of ALK-rearranged non-small cell lung cancer (ID 2824)

      09:30 - 16:30  |  Author(s): M. Masuda

      • Abstract

      Background
      Crizotinib(Xalkori®) was developed as a medicine for anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Multi institutes studies established its efficacy and safety for advanced lung carcinoma. After crizotinib release in Japan, there has been no report about usage of crizotinib for postoperative recurrence of lung cancer. We have four patients with postoperative recurrence of ALK-rearranged NSCLC who were treated with crizotinib. We herein report the efficacy and safety of the treatment.

      Methods
      not applicable

      Results
      Case report ALK-rearrangements were confirmed by FISH examination from surgical specimen in all four patients. Histological diagnoses were pulmonary adenocarcinoma in all cases. Case 1. A 62-year-old man underwent the right middle and lower lobectomy (pT3N2M0) followed by adjuvant chemotherapy with platinum doublet. He had a mediastinum lymph node relapse six months after the operation. Crizotinib was administered as the 2[nd] line. A long stable disease (SD, six months) was obtained in this patient. Case 2. A 62-year-old woman underwent the right upper and middle lobectomy (pT2aN2M1a) followed by adjuvant chemotherapy with platinum doublet. She had multiple lung metastases thirty-one months after the operation. Progressive disease (PD) was detected after four courses of platinum doublet. Crizotinib was administered as the 5[th] line and partial response (PR) was obtained over 5 months. Case 3. A 63-year-old man underwent preoperative chemotherapy followed by the right upper lobectomy (ypT3N2M0). He received an adjuvant chemotherapy with platinum doublet. He developed brain metastases five months after the operation. Crizotinib was administered one month as the 4[th] line, and PR was obtained. Case 4. An 83-year-old woman underwent the left lower lobe wedge resection. (pT2aNXM1a) followed by four regimens of chemotherapy, resulting in PD. Crizotinib was administered as the 5[th] line. The side effects with increase in body weight (+4kg, Grade1), leg edema (Grade 2) and liver dysfunction (Grade 1) deveroped on the 7[th] day. Her symptoms quickly disappeared after discontinue of crizotinib. Another regimen chemotherapy was administered because she rejected restart of the crizotinib treatment.

      Conclusion
      In the efficacies of the crizotinib treatment, two cases were PR, one case was SD and one case was drop out. The crizotinib was effective in two cases which were PD with other regimen treatments. Crizotinib has possibilities of giving dramatic clinical response in ALK-rearranged NSCLC patients. In safeties of the crizotinib treatment, no adverse event was occurred in three cases and Grade 2 adverse in one case. There have been no serious complications. Crizotinib treatments in ALK-rearranged NSCLC patients have great possibilities of having a clinical benefit. Crizotinib can also be effective and safe in postoperative recurrence of ALK-rearranged NSCLC patients. We reacknowledge an importance of molecular targeted therapy that creates dramatic clinical effects within a short time period. Further observation and accumulation of cases will be necessary to evaluate the clinical effectiveness of this treatment in postoperative recurrence of ALK-rearranged NSCLC patients.