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P1.05-055 Risk Factors of Postoperative Recurrence in Stage IA and IB Patients
S648
P1.05-054 Adjuvant Chemotherapy Uptake in Patients with NSCLC after Complete Resection: Single Institution/Single Area Experience Topic: Neoadjuvant and Adjuvant Chemotherapy Vitezslav Kolek,1 Ivona Grygarkova,1 Juraj Kultan,1 Petr Jakubec,1 Marek Szkorupa,2 Jiri Klein,2 Cestmir Neoral,2 Josef Skarda,3 Tomas Tichy,3 Zdenek Kolar3 1Dept. of Respiratoty Medicine, University Hospital, Olomouc/Czech Republic, 2Dept. of Surgery, University Hospital, Olomouc/Czech Republic, 3Dept. of Molecular Pathology, University Hospital, Olomouc/Czech Republic Background: Adjuvant chemotherapy (AC) is recommended in patients (pts) with stages IB (tumor of 4 cm in diameter), IIA, IIB, and IIIA of non-small cell lung cancer (NSCLC) after complete resection. According to metaanalyses it prolongs survival of pts in good PS and age less than 75 years. The selection of patients is influenced by the limited profit of AC, possible toxicity and the lack of predictive biomarkers. There are only few retrospective studies describing routine utilization of AC in specified areas. Presented AC uptake in stages II and III varies from 20 % to 24% in Canada and USA. Methods: A retrospective study of AC uptake in pts with NSCLC from a Moravian region with 600.000 inhabitants was conducted, evaluation period was 2006-2013. Treatment strategy of all patients was discussed by surgeons and pneumo-oncologists on the interdisciplinary tumor boards before and after surgery. Uptake and compliance of AC was evaluated according to age, sex, TNM stages, type of surgery and other cofactors. AC was given in regimens using doublets of platinum with vinorelbine (rarely gemcitabine or paclitaxel). Vinorelbine was applied both intravenously (25 mg/m2) and orally (60 - 80 mg/m2). The choice of cisplatinum (80mg/m2) or carboplatinum (AUC 5) was based on patient preference, PS and comorbidities. Results: Out of all 1557 pts with lung cancer, NSCLC was present in 1293 pts. 308 pts underwent curative-intent surgery and complete resection was achieved in 295 pts. 226 pts were pts with stages IB, II and IIIA and AC was applied in 183 pts (80.1%), in 34 (18.6 %) pts together with neoadjuvant chemotherapy. AC was not applied in 43 (19.9 %) pts after radical surgery due to worse PS, comorbidities, complications after surgery or patient’s refusal. The mean age of pts with AC was 65 years, 66,7% were men, 48,9 % women, 49,9 % were current smokers,
Journal of Thoracic Oncology
Vol. 12 No. 1S
40,0% ex-smokers and 10,1 % non-smokers. Age, sex and smoking habits were not statistically different between pts with and without AC. Compliance with AC was very good, 82% of pts accomplished planned therapy. Conclusion: The optimal uptake of AC in routine practice depends on the intensive communication between the patient, surgeons and pneumocologists. The individual decision is important in a context to the patients’ health status, tumor parameters and the potential risk/ benefit of therapy. Study was supported by grant AZV 16-32318A. Keywords: non-small cell lung cancer, surgery, adjuvant chemotherapy, utilization in practice
P1.05-055 Risk Factors of Postoperative Recurrence in Stage IA and IB Patients Topic: Recurrence Fumihiko Hoshi,1 Akira Sakurada,1 Toru Hasumi,2 Tetsu Sado,2 Masafumi Noda,1 Yasushi Matsuda,1 Shunsuke Eba,1 Hideki Mitomo,1 Takeo Togo,1 Masato Katahira,1 Yoshinori Okada1 1Tohoku University Hospital, Miyagi/Japan, 2Sendai Medical Center, Sendai/Japan Background: The 5-year survival rates of the patients with pathological stage IA and IB NSCLC have been reported 86-93% and 67-84%, respectively. Among stage I disease, patients with stage IA of tumor diameter over 20 mm as well as stage IB are recommended to take oral UFT as adjuvant chemotherapy for 2 years in Japan. Even after complete resection and such adjuvant therapy, we still observe recurrence at a certain rate. Identifying clinicopathological factors which is associated with recurrence would be beneficial to establish alternative strategy. The purpose of this study is to identify the predictive factors for recurrence in the patients with stage I NSCLC. Methods: A total of 742 stage I NSCLC patients who underwent complete resection in our hospital from 1996 to 2012 were retrospectively analyzed. Medical records of these patients were reviewed carefully. The median age was 66.4 years with 512 stage IA and 281 stage IB. Histopathologically, there were 590 adenocarcinoma, 150 squamous cell carcinoma, 32 large cell carcinoma, and 21 other histology cases. Surgical procedure was segmentectomy, lobectomy, and pneumonectomy for 46, 588, and 8 patients, respectively. Clinicopathological factors such as smoking history, histology, pathological vascular invasion (v), and lymphatic vessel invasion (ly) were analyzed.
January 2017
Results: Recurrence occurred in 132 cases. Multivariate analysis showed that T factor, v(+), ly(+), and smoking history have statistical significance with recurrence. n pT1a and T2a cases, there were no statistical significance between recurrence and pathological ly(+) and/or v(+). But only in T1b cases, ly(+) and/or v(+) had statistical significance with recurrence. Conclusion: We identified that T factor, v, ly, and smoking history were predictive factors for recurrence in stage IA and IB NSCLC patients. Because of good prognosis, pT1b patients whose both v and ly were negative may not take UFT as adjuvant chemotherapy. Keywords: NSCLC, stage IA and stage IB, recurrence
P1.05-056 Increased Risk of Postoperative Recurrence in EGFR-Positive Stage IA to IB Invasive Lung Adenocarcinoma Topic: Recurrence Masaoki Ito,1 Yoshihiro Miyata,1 Kei Kushitani,2 Tomoharu Yoshiya,1 Yasuhiro Tsutani,1 Kazuo Konishi,1 Yukio Takeshima,2 Morihito Okada1 1 Department of Thoracic Surgery, Hiroshima University Hospital, Hiroshima/Japan, 2Department of Pathology, Hiroshima University Hospital, Hiroshima/Japan Background: Somatic mutations of EGFR represent one of the most frequent genetic aberrations in lung adenocarcinoma and response to tyrosine kinase inhibitors (TKIs) has been favorable in EGFR-positive and advanced lung adenocarcinoma patients. The prognostic significance of EGFR mutations as oncogenic driver mutations in early-stage lung adenocarcinoma has yet to be determined. We aimed to evaluate the oncological significance of EGFR mutations in early-stage lung adenocarcinoma. Methods: Four hundred and seventy-three consecutive lung adenocarcinoma patients who underwent surgical resection for pathological N0M0 disease, between January 2007 and December 2013, were retrospectively reviewed. The prognostic significance of EGFR mutation status was evaluated in 407 cases from these patients. Overall survival (OS) and recurrence-free interval (RFI) curves were estimated using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Results: There was no statistical significance in the 5year OS (89.3 vs. 95.3%, P ¼ .20, HR ¼ 1.605) or RFI (86.5 vs. 93.5%, P ¼ .06, HR ¼ 1.956) rates between the
Abstracts
S649
EGFR-positive (n¼183) and EGFR-negative (n¼224) groups. Considering the risk of recurrence and positive EGFR mutation status, OS and RFI rates were subsequently calculated among specific histological subtypes. After adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive mucinous adenocarcinoma (IMA) cases were excluded, all analyzed cases were 5.0 cm in tumor diameter and were classified as pathological Stage IA-IB. Among specific histological subtypes, the 5-year RFI (81.5 vs. 92.4%, P ¼ .04, HR ¼ 2.160) but not OS rate (86.8 vs. 94.3%, P ¼ .31, HR ¼ 1.499) was significantly poorer in EGFR-positive cases compared to EGFR-negative cases. Univariate analysis, excluding AIS, MIA, and IMA, identified a pathological tumor size of >3.0 cm, a highly malignant subtype (micropapillary or solid predominant adenocarcinoma), pleural/lymphatic/vascular invasion, and a positive EGFR mutation status as significant negative predictive factors for RFI. Multivariate analysis confirmed pleural invasion and a positive EGFR mutation status as independent negative predictive factors for RFI. Conclusion: EGFR mutation status is a predictive factor for postoperative recurrence in early-stage lung adenocarcinoma, with the exception of AIS, MIA, and IMA. The risk of recurrence should be considered with EGFR mutation status and predominant histological subtype in resected early-stage lung adenocarcinoma patients. Keywords: Early-stage, Surgery, EGFR, Adenocarcinoma
P1.05-057 Prediction of Early Recurrence in Patients with Stage I and II Non-Small Cell Lung Cancer Using FDG PET Quantification Topic: Recurrence Michael Arvanitakis,1 Irene Burger,2 Seraina Steiger,3 Beate Sick,4 Walter Weder,1 Sven Hillinger1 1Thoracic Surgery, University Hospital, Zürich/Switzerland, 2Nuclear Medicine and Radiology, University Hospital, Zürich/ Switzerland, 3Radiology, University Hospital, Zürich/ Switzerland, 4Engineering, Biostatistics, Zurich University of Applied Sciences, Winterthur/Switzerland Background: Although surgical resection remains the optimal treatment for early-stage NSCLC, up to 50% of patients with stage I and II relapse and die within 5 years after curative resection. Therefore prognostic markers are important as these patients might benefit from adjuvant therapy. The goal of this study was to evaluate established PET quantification metrics
P1.05-054 Adjuvant Chemotherapy Uptake in Patients with NSCLC after Complete Resection: Single Institution/Single Area Experience Topic: Neoadjuvant and Adjuvant Chemotherapy Vitezslav Kolek,1 Ivona Grygarkova,1 Juraj Kultan,1 Petr Jakubec,1 Marek Szkorupa,2 Jiri Klein,2 Cestmir Neoral,2 Josef Skarda,3 Tomas Tichy,3 Zdenek Kolar3 1Dept. of Respiratoty Medicine, University Hospital, Olomouc/Czech Republic, 2Dept. of Surgery, University Hospital, Olomouc/Czech Republic, 3Dept. of Molecular Pathology, University Hospital, Olomouc/Czech Republic Background: Adjuvant chemotherapy (AC) is recommended in patients (pts) with stages IB (tumor of 4 cm in diameter), IIA, IIB, and IIIA of non-small cell lung cancer (NSCLC) after complete resection. According to metaanalyses it prolongs survival of pts in good PS and age less than 75 years. The selection of patients is influenced by the limited profit of AC, possible toxicity and the lack of predictive biomarkers. There are only few retrospective studies describing routine utilization of AC in specified areas. Presented AC uptake in stages II and III varies from 20 % to 24% in Canada and USA. Methods: A retrospective study of AC uptake in pts with NSCLC from a Moravian region with 600.000 inhabitants was conducted, evaluation period was 2006-2013. Treatment strategy of all patients was discussed by surgeons and pneumo-oncologists on the interdisciplinary tumor boards before and after surgery. Uptake and compliance of AC was evaluated according to age, sex, TNM stages, type of surgery and other cofactors. AC was given in regimens using doublets of platinum with vinorelbine (rarely gemcitabine or paclitaxel). Vinorelbine was applied both intravenously (25 mg/m2) and orally (60 - 80 mg/m2). The choice of cisplatinum (80mg/m2) or carboplatinum (AUC 5) was based on patient preference, PS and comorbidities. Results: Out of all 1557 pts with lung cancer, NSCLC was present in 1293 pts. 308 pts underwent curative-intent surgery and complete resection was achieved in 295 pts. 226 pts were pts with stages IB, II and IIIA and AC was applied in 183 pts (80.1%), in 34 (18.6 %) pts together with neoadjuvant chemotherapy. AC was not applied in 43 (19.9 %) pts after radical surgery due to worse PS, comorbidities, complications after surgery or patient’s refusal. The mean age of pts with AC was 65 years, 66,7% were men, 48,9 % women, 49,9 % were current smokers,
Journal of Thoracic Oncology
Vol. 12 No. 1S
40,0% ex-smokers and 10,1 % non-smokers. Age, sex and smoking habits were not statistically different between pts with and without AC. Compliance with AC was very good, 82% of pts accomplished planned therapy. Conclusion: The optimal uptake of AC in routine practice depends on the intensive communication between the patient, surgeons and pneumocologists. The individual decision is important in a context to the patients’ health status, tumor parameters and the potential risk/ benefit of therapy. Study was supported by grant AZV 16-32318A. Keywords: non-small cell lung cancer, surgery, adjuvant chemotherapy, utilization in practice
P1.05-055 Risk Factors of Postoperative Recurrence in Stage IA and IB Patients Topic: Recurrence Fumihiko Hoshi,1 Akira Sakurada,1 Toru Hasumi,2 Tetsu Sado,2 Masafumi Noda,1 Yasushi Matsuda,1 Shunsuke Eba,1 Hideki Mitomo,1 Takeo Togo,1 Masato Katahira,1 Yoshinori Okada1 1Tohoku University Hospital, Miyagi/Japan, 2Sendai Medical Center, Sendai/Japan Background: The 5-year survival rates of the patients with pathological stage IA and IB NSCLC have been reported 86-93% and 67-84%, respectively. Among stage I disease, patients with stage IA of tumor diameter over 20 mm as well as stage IB are recommended to take oral UFT as adjuvant chemotherapy for 2 years in Japan. Even after complete resection and such adjuvant therapy, we still observe recurrence at a certain rate. Identifying clinicopathological factors which is associated with recurrence would be beneficial to establish alternative strategy. The purpose of this study is to identify the predictive factors for recurrence in the patients with stage I NSCLC. Methods: A total of 742 stage I NSCLC patients who underwent complete resection in our hospital from 1996 to 2012 were retrospectively analyzed. Medical records of these patients were reviewed carefully. The median age was 66.4 years with 512 stage IA and 281 stage IB. Histopathologically, there were 590 adenocarcinoma, 150 squamous cell carcinoma, 32 large cell carcinoma, and 21 other histology cases. Surgical procedure was segmentectomy, lobectomy, and pneumonectomy for 46, 588, and 8 patients, respectively. Clinicopathological factors such as smoking history, histology, pathological vascular invasion (v), and lymphatic vessel invasion (ly) were analyzed.
January 2017
Results: Recurrence occurred in 132 cases. Multivariate analysis showed that T factor, v(+), ly(+), and smoking history have statistical significance with recurrence. n pT1a and T2a cases, there were no statistical significance between recurrence and pathological ly(+) and/or v(+). But only in T1b cases, ly(+) and/or v(+) had statistical significance with recurrence. Conclusion: We identified that T factor, v, ly, and smoking history were predictive factors for recurrence in stage IA and IB NSCLC patients. Because of good prognosis, pT1b patients whose both v and ly were negative may not take UFT as adjuvant chemotherapy. Keywords: NSCLC, stage IA and stage IB, recurrence
P1.05-056 Increased Risk of Postoperative Recurrence in EGFR-Positive Stage IA to IB Invasive Lung Adenocarcinoma Topic: Recurrence Masaoki Ito,1 Yoshihiro Miyata,1 Kei Kushitani,2 Tomoharu Yoshiya,1 Yasuhiro Tsutani,1 Kazuo Konishi,1 Yukio Takeshima,2 Morihito Okada1 1 Department of Thoracic Surgery, Hiroshima University Hospital, Hiroshima/Japan, 2Department of Pathology, Hiroshima University Hospital, Hiroshima/Japan Background: Somatic mutations of EGFR represent one of the most frequent genetic aberrations in lung adenocarcinoma and response to tyrosine kinase inhibitors (TKIs) has been favorable in EGFR-positive and advanced lung adenocarcinoma patients. The prognostic significance of EGFR mutations as oncogenic driver mutations in early-stage lung adenocarcinoma has yet to be determined. We aimed to evaluate the oncological significance of EGFR mutations in early-stage lung adenocarcinoma. Methods: Four hundred and seventy-three consecutive lung adenocarcinoma patients who underwent surgical resection for pathological N0M0 disease, between January 2007 and December 2013, were retrospectively reviewed. The prognostic significance of EGFR mutation status was evaluated in 407 cases from these patients. Overall survival (OS) and recurrence-free interval (RFI) curves were estimated using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Results: There was no statistical significance in the 5year OS (89.3 vs. 95.3%, P ¼ .20, HR ¼ 1.605) or RFI (86.5 vs. 93.5%, P ¼ .06, HR ¼ 1.956) rates between the
Abstracts
S649
EGFR-positive (n¼183) and EGFR-negative (n¼224) groups. Considering the risk of recurrence and positive EGFR mutation status, OS and RFI rates were subsequently calculated among specific histological subtypes. After adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive mucinous adenocarcinoma (IMA) cases were excluded, all analyzed cases were 5.0 cm in tumor diameter and were classified as pathological Stage IA-IB. Among specific histological subtypes, the 5-year RFI (81.5 vs. 92.4%, P ¼ .04, HR ¼ 2.160) but not OS rate (86.8 vs. 94.3%, P ¼ .31, HR ¼ 1.499) was significantly poorer in EGFR-positive cases compared to EGFR-negative cases. Univariate analysis, excluding AIS, MIA, and IMA, identified a pathological tumor size of >3.0 cm, a highly malignant subtype (micropapillary or solid predominant adenocarcinoma), pleural/lymphatic/vascular invasion, and a positive EGFR mutation status as significant negative predictive factors for RFI. Multivariate analysis confirmed pleural invasion and a positive EGFR mutation status as independent negative predictive factors for RFI. Conclusion: EGFR mutation status is a predictive factor for postoperative recurrence in early-stage lung adenocarcinoma, with the exception of AIS, MIA, and IMA. The risk of recurrence should be considered with EGFR mutation status and predominant histological subtype in resected early-stage lung adenocarcinoma patients. Keywords: Early-stage, Surgery, EGFR, Adenocarcinoma
P1.05-057 Prediction of Early Recurrence in Patients with Stage I and II Non-Small Cell Lung Cancer Using FDG PET Quantification Topic: Recurrence Michael Arvanitakis,1 Irene Burger,2 Seraina Steiger,3 Beate Sick,4 Walter Weder,1 Sven Hillinger1 1Thoracic Surgery, University Hospital, Zürich/Switzerland, 2Nuclear Medicine and Radiology, University Hospital, Zürich/ Switzerland, 3Radiology, University Hospital, Zürich/ Switzerland, 4Engineering, Biostatistics, Zurich University of Applied Sciences, Winterthur/Switzerland Background: Although surgical resection remains the optimal treatment for early-stage NSCLC, up to 50% of patients with stage I and II relapse and die within 5 years after curative resection. Therefore prognostic markers are important as these patients might benefit from adjuvant therapy. The goal of this study was to evaluate established PET quantification metrics