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P3.01-079 Evaluating the Roles of Neoadjuvant and Adjuvant Chemotherapy for Treating Patients with Stage IIIa (N2) Lung Cancer
S2232 values between 0-1. Where 0 represents a health state similar to death and 1 represents a perfect health state. Result: The restricted mean health state duration in months for each state with its 95% CI for each arm, the difference between the 2 arms for each health state with its 95%CI and corresponding p-value will be provided. The results of threshold utility analysis with the corresponding QTWiST difference between the 2 arms with p-value would be presented. Conclusion: LBA: Not applicable. Keywords: EGFR mutation, NSCLC, QTWiST
P3.01-077 Effectiveness of Methylnaltrexone Bromide in OpioidInduced Constipation in Advanced NSCLC Patients I. Dimitroulis,1 P. Peristeris,2 M. Toumbis2 16th Pulmonary Dept., Sotiria Hospital for Thoracic Diseases, Athens/GR, 2Sotiria Hospital for Thoracic Diseases, Athens/GR Background: Methylnaltrexone Bromide (MB) is a selective antagonist of opioid binding at the mu-receptor (m or MOR receptor). Constipation is a quite common side effect in Non-Small-Cell-Lung-Cancer (NSCLC) patients receiving opioids for chronic pain, usually due to skeletal metastases. We set out to investigate if MB is effective in those patients who received opioids and complained of constipation. Method: Sixtyeight NSCLC patients with a life expectancy of at least three months were recruited for our study after providing written consent. All patients received either fentanyl as a transdermal patch, in its inhaled form or per os. Patients were randomized (1:1) to four weeks of treatment with either MB 12mg/0.6ml (n¼22) administered subcutaneously (sc) or a placebo, on alternate days. We recorded the number of patients who defecated within four hours of the MB or placebo injection, and the number of patients needing a second dose of MB or placebo within six hours from the first dose. We recorded the side effects of this treatment. Patients were not allowed to use other laxatives. Result: In the MB group after one injection, fifty one patients (75%) had a bowel movement within four hours compared to nine placebo patients (13%), p¼0.02. Fifteen patients in the MB group had a bowel movement after two or more doses of MB, raising the percentage of patients who responded to MB to 96%. The more severe the constipation, the higher the response with MB. The overall rate of adverse events was similar in the MB (43%) and placebo groups (42%). In the MB group, the most commonly reported adverse events were abdominal pain (16%), flatulence (16%), vomiting (11%), and nausea (13%). Most treatment related adverse events were rated as mild or moderate by the patients. Discontinuation due to adverse events occurred in 5% and 6% of patients in the MB and placebo groups, respectively. Conclusion: Methylnaltrexone Bromide has been shown to be superior to placebo in achieving defecation within a short time, in NSCLC patients with opioid-induced constipation, The more severe constipation, the higher the response with MB. There were no serious adverse events. We conclude that Methylnaltrexone Bromide is effective, safe and superior to other commonly used laxatives. Keywords: Opioids, Constipation, Methylnaltrexone Bromide
P3.01-078 Outcome of Stage IIIb Non-small Cell Lung Cancer (NSCLC) Patients e A Single Tertiary Center Experience T. Mehmood Radiation Oncology, Northwest General Hospital and Research Center, Peshawar/PK Background: The optimal treatment strategy for Stage IIIB NSCLC patients with a T4N0-1 tumor is a matter of debate. In prospective combined modality series including surgery, the median overall
Journal of Thoracic Oncology
Vol. 12 No. 11S2
survival (OS) is approximately 24 months. We hypothesized that results comparable to regimens including surgery can be achieved with concurrent chemoradiation in this patient group. Method: In our retrospectively collected database of NSCLC patients, all patients with T4 (mediastinal invasion) N0-1 NSCLC receiving concurrent chemoradiation were included. One patient had a recurrence after previous pneumonectomy. All patients were given 3 cycles of chemotherapy (cisplatin and etoposide). Radiotherapy (RT) was started at the 2nd course of chemotherapy. OS was calculated from date of diagnosis (Kaplan-Meier method). Toxicity was scored according to CTCAEv3.0. Result: 42 patients (8 female, 34 male) with a median age of 62.5 ± 9 years (44-80 years) were included from January 2005 until December 2009. Stage distribution: 86% T4N0 (n¼36), 14% T4N1 (n¼6). The maximal tumor dose was 66 Gy using conventional fractionation. The median prescribed mean lung dose was 15 ± 4.4 Gy (5.03 -19.9 Gy). Acute toxicity: 1 patient experienced grade 3 dyspnea during RT. Grade 3 dysphagia occurred in 5 patients (12%) during RT requiring tube feeding in 3 of these patients (7%). Dysphagia persisted later than 1 month after RT in 1 patient (2%). Grade 3 dysphagia only occurred in patients treated concurrently. Grade 3 cough occurred in 1 patient during RT, no patient experienced grade 3 cough 1 month after RT. 2 patients died within 3 months after start of RT, one due to myocardial infarction, one of unknown causes. Severe late toxicity was not present: no grade 3 complications more than 3 months after the end of radiotherapy. With a median follow-up of 42 months, the median OS for the whole group is 34 months (95% CI 24-43 months). 2-year OS survival is 55%. Conclusion: Concurrent accelerated chemoradiation using an individualized dose prescription is a valid treatment strategy for stage IIIb, T4N0-1 NSCLC patients yielding very promising OS results with low toxicity. Keywords: NSCLC
P3.01-079 Evaluating the Roles of Neoadjuvant and Adjuvant Chemotherapy for Treating Patients with Stage IIIa (N2) Lung Cancer L. Yong, S. Kuo, P. Huang, M. Lin, K. Chen, J. Lee Department of Surgery, National Taiwan University, Taipei/TW Background: The survival benefit of systemic chemotherapy has been demonstrated for treating patients with stage IIIa (N2+) lung cancer. The NCCN guideline recommends induction chemotherapy with or without irradiation followed by surgery for those patients if no disease progression was noted after induction therapy. However, there are also studies revealed the survival benefit of adjuvant chemotherapy for patients with N2+ IIIa disease. The current study compared the survival results of neoadjuvant (before surgery, BS) and adjuvant (after surgery, AS) chemotherapy plus surgical resection for the patients with non-small cell lung cancer with N2+ stage IIIa disease. Method: There were 217 patients with Stage IIIa N2+ who received surgery resection in the recent decade in our hospital, with a mean follow-up duration of 44 months. The overall survival time was evaluated and compared between these three groups of patients. Result: There were 62, 44 and 111 patients without chemotherapy(C/T) (Nil) or C/T given as neoadjuvant (BS) and adjuvant (AS) setting respectively. There were more patients with advanced age in the Nil and AS groups and more patients with AS group have received sublobal resection (p<0.01 respectively) as compared to the patients of BS group. The mean survival duration after surgery for the patients of AS and BS groups was 57.6 and 50.4 months respectively which was significantly longer than those patients of Nil group (MST: 26.4 months: p<0.001 respectively). Multivariate analysis revealed the addition of chemotherapy as a single prognostic factor of the patients. However, there was no significant difference of
November 2017
Abstracts
S2233
survival duration between the patients of AS and BS groups. Conclusion: Chemotherapy given both as adjuvant or neoadjuvant setting can provide a survival benefit for the patients with stage IIIa N2+ non-small cell lung cancer after surgery. No statistical difference was observed about the survival duration for these two groups of patients. Keywords: chemotherapy, NSCLC, Advanced NSCLS
Fig 1. Overall survival of pathological N2 according to type of resection.
P3.01-080 Overall Survival (OS) of Pathological N2 Non-Small Cell Lung Cancer (NSCLC) After Surgical Resection E. Bourdages-Pageau,1 A. Vieira,2 C. Labbé,2 P. Ugalde Figueroa3 1 Laval University, Quebec/QC/CA, 2Thoracic Surgery, Institut Universitaire de Cardiologie Et de Pneumologie de Québec (Iucpq), Québec/CA, 3Thoracic Surgery, Institut Universitaire de Cardiologie Et Pneumologie de Quebec, Quebec/QC/CA Background: Despite complete pre-operative staging, incidental N2 disease is still found during surgical resection of NSCLC. Proceeding with resection versus aborting the operation to treat with definitive chemotherapy and radiotherapy is controversial. The aim of the current study was to evaluate survival of pathological N2 disease after complete resection. Method: The Institut de Cardiologie et Pneumologie de Quebec Biobank was queried for all patients with pathological N2 NSCLC who underwent complete (R0) surgical resection either by lobectomy, bilobectomy or pneumonectomy between January 2000 and February 2017. Survival was examined using the Kaplan-Meier method with log rank analysis. Significance was set at p0.05. Result: We identified 224 eligible patients; 119 (53%) were male, mean age was 63±9, there were 143 (64%) adenocarcinoma and 60 (27%) squamous cell carcinoma. Regarding surgical modality, 156 (70%) patients underwent lobectomy or bilobectomy and 68 (30%) pneumonectomy. The 30-day mortality of the cohort was 3% (5 pneumonectomy and 2 lobectomy). During 17 years of follow-up, 142 (63%) patients died, including 87 (61%) in the lobectomy/bilobectomy group and 55 (39%) in the pneumonectomy group. Among all deaths, 105 (74%) were cancer-related. Median OS of the entire cohort was 2.6 y (CI 1.9-4.4). In the univariate analysis cox model, median OS was shorter for pneumonectomy than lobectomy/bilobectomy (2,1 years [1,6-2,6) vs 4,4 years [2,2-5,8]), HR 1.54 (CI 1.09 e 2.16, p¼0.01; figure 1). However, when only considering cancer-related deaths, the difference was not statistically significant (p¼0.95). Conclusion: In our institutional database study, median OS after surgical resection of N2 NSCLC was 2.6y. Pneumonectomy is indicated as cancer cure treatment however, major efforts should be made to decrease peri-operative morbidity and mortality.
P3.01-081 Overall Survival (OS) of Locally Advanced Non-Small Cell Lung Cancer (NSCLC) After Negative Invasive Mediastinal Staging E. Bourdages-Pageau,1 A. Vieira,2 C. Labbé,2 P. Ugalde Figueroa3 Laval University, Quebec/QC/CA, 2Thoracic Surgery, Institut Universitaire de Cardiologie Et de Pneumologie de Québec (Iucpq), Québec/CA, 3Thoracic Surgery, Institut Universitaire de Cardiologie Et Pneumologie de Quebec, Quebec/QC/CA
1
Background: According to current guidelines, invasive pre-operative staging should be performed with endoscopic ultrasound in NSCLC in suspected N2 disease. Due to its higher negative predictive value, in case of PET positive, CT enlarged mediastinal lymph nodes or central tumors, mediastinoscopy remains indicated when EBUS staging is negative. The aim of the current study was to evaluate OS of patients with locally advanced NSCLC who underwent surgical resection after negative EBUS and mediastinoscopy. Method: The Institut de Cardiologie et Pneumologie de Quebec Biobank was queried for all patients with high probability of N2 disease or central tumors with negative EBUS and mediastinoscopy that underwent complete surgical resection (R0) between March 2009 and February 2017. Survival was examined using the Kaplan-Meier method with log rank analysis. Significance was set at p0.05. Result: We identified 88 eligible patients (Table 1); 56 (64%) were male, mean age was 65±9 and 50% of the cases were adenocarcinoma. Regarding surgical modality, 1 (1%) patient underwent sublobar resection, 65 (74%) lobectomy or bilobectomy and 22 (25%) pneumonectomy. Among these, there were 11 (13%) pathological N2 cases. There was no 30-day mortality. During 8 years of follow-up, 30 patients died, including 20 (31%) in the lobectomy/ bilobectomy group compared to 9 (41%) in the pneumonectomy group. We then identified 16 (80%) cancer-related deaths in the lobectomy/bilobectomy and 7 (78%) in the pneumonectomy group. Median OS of the entire cohort was 5.7 years, with no difference between groups (HR 1.29, CI 0.58-2.87, p¼0.53). Conclusion: In our institutional database, patients locally advanced NSCLC had 13% incidence of pathological N2 disease and the OS was 5.7y. Our data supports surgical complete resection either by lobectomy or pneumonectomy in this group of patients with locally advanced disease. Keywords: mediastinal staging, pneumonectomy and lobectomy
P3.01-077 Effectiveness of Methylnaltrexone Bromide in OpioidInduced Constipation in Advanced NSCLC Patients I. Dimitroulis,1 P. Peristeris,2 M. Toumbis2 16th Pulmonary Dept., Sotiria Hospital for Thoracic Diseases, Athens/GR, 2Sotiria Hospital for Thoracic Diseases, Athens/GR Background: Methylnaltrexone Bromide (MB) is a selective antagonist of opioid binding at the mu-receptor (m or MOR receptor). Constipation is a quite common side effect in Non-Small-Cell-Lung-Cancer (NSCLC) patients receiving opioids for chronic pain, usually due to skeletal metastases. We set out to investigate if MB is effective in those patients who received opioids and complained of constipation. Method: Sixtyeight NSCLC patients with a life expectancy of at least three months were recruited for our study after providing written consent. All patients received either fentanyl as a transdermal patch, in its inhaled form or per os. Patients were randomized (1:1) to four weeks of treatment with either MB 12mg/0.6ml (n¼22) administered subcutaneously (sc) or a placebo, on alternate days. We recorded the number of patients who defecated within four hours of the MB or placebo injection, and the number of patients needing a second dose of MB or placebo within six hours from the first dose. We recorded the side effects of this treatment. Patients were not allowed to use other laxatives. Result: In the MB group after one injection, fifty one patients (75%) had a bowel movement within four hours compared to nine placebo patients (13%), p¼0.02. Fifteen patients in the MB group had a bowel movement after two or more doses of MB, raising the percentage of patients who responded to MB to 96%. The more severe the constipation, the higher the response with MB. The overall rate of adverse events was similar in the MB (43%) and placebo groups (42%). In the MB group, the most commonly reported adverse events were abdominal pain (16%), flatulence (16%), vomiting (11%), and nausea (13%). Most treatment related adverse events were rated as mild or moderate by the patients. Discontinuation due to adverse events occurred in 5% and 6% of patients in the MB and placebo groups, respectively. Conclusion: Methylnaltrexone Bromide has been shown to be superior to placebo in achieving defecation within a short time, in NSCLC patients with opioid-induced constipation, The more severe constipation, the higher the response with MB. There were no serious adverse events. We conclude that Methylnaltrexone Bromide is effective, safe and superior to other commonly used laxatives. Keywords: Opioids, Constipation, Methylnaltrexone Bromide
P3.01-078 Outcome of Stage IIIb Non-small Cell Lung Cancer (NSCLC) Patients e A Single Tertiary Center Experience T. Mehmood Radiation Oncology, Northwest General Hospital and Research Center, Peshawar/PK Background: The optimal treatment strategy for Stage IIIB NSCLC patients with a T4N0-1 tumor is a matter of debate. In prospective combined modality series including surgery, the median overall
Journal of Thoracic Oncology
Vol. 12 No. 11S2
survival (OS) is approximately 24 months. We hypothesized that results comparable to regimens including surgery can be achieved with concurrent chemoradiation in this patient group. Method: In our retrospectively collected database of NSCLC patients, all patients with T4 (mediastinal invasion) N0-1 NSCLC receiving concurrent chemoradiation were included. One patient had a recurrence after previous pneumonectomy. All patients were given 3 cycles of chemotherapy (cisplatin and etoposide). Radiotherapy (RT) was started at the 2nd course of chemotherapy. OS was calculated from date of diagnosis (Kaplan-Meier method). Toxicity was scored according to CTCAEv3.0. Result: 42 patients (8 female, 34 male) with a median age of 62.5 ± 9 years (44-80 years) were included from January 2005 until December 2009. Stage distribution: 86% T4N0 (n¼36), 14% T4N1 (n¼6). The maximal tumor dose was 66 Gy using conventional fractionation. The median prescribed mean lung dose was 15 ± 4.4 Gy (5.03 -19.9 Gy). Acute toxicity: 1 patient experienced grade 3 dyspnea during RT. Grade 3 dysphagia occurred in 5 patients (12%) during RT requiring tube feeding in 3 of these patients (7%). Dysphagia persisted later than 1 month after RT in 1 patient (2%). Grade 3 dysphagia only occurred in patients treated concurrently. Grade 3 cough occurred in 1 patient during RT, no patient experienced grade 3 cough 1 month after RT. 2 patients died within 3 months after start of RT, one due to myocardial infarction, one of unknown causes. Severe late toxicity was not present: no grade 3 complications more than 3 months after the end of radiotherapy. With a median follow-up of 42 months, the median OS for the whole group is 34 months (95% CI 24-43 months). 2-year OS survival is 55%. Conclusion: Concurrent accelerated chemoradiation using an individualized dose prescription is a valid treatment strategy for stage IIIb, T4N0-1 NSCLC patients yielding very promising OS results with low toxicity. Keywords: NSCLC
P3.01-079 Evaluating the Roles of Neoadjuvant and Adjuvant Chemotherapy for Treating Patients with Stage IIIa (N2) Lung Cancer L. Yong, S. Kuo, P. Huang, M. Lin, K. Chen, J. Lee Department of Surgery, National Taiwan University, Taipei/TW Background: The survival benefit of systemic chemotherapy has been demonstrated for treating patients with stage IIIa (N2+) lung cancer. The NCCN guideline recommends induction chemotherapy with or without irradiation followed by surgery for those patients if no disease progression was noted after induction therapy. However, there are also studies revealed the survival benefit of adjuvant chemotherapy for patients with N2+ IIIa disease. The current study compared the survival results of neoadjuvant (before surgery, BS) and adjuvant (after surgery, AS) chemotherapy plus surgical resection for the patients with non-small cell lung cancer with N2+ stage IIIa disease. Method: There were 217 patients with Stage IIIa N2+ who received surgery resection in the recent decade in our hospital, with a mean follow-up duration of 44 months. The overall survival time was evaluated and compared between these three groups of patients. Result: There were 62, 44 and 111 patients without chemotherapy(C/T) (Nil) or C/T given as neoadjuvant (BS) and adjuvant (AS) setting respectively. There were more patients with advanced age in the Nil and AS groups and more patients with AS group have received sublobal resection (p<0.01 respectively) as compared to the patients of BS group. The mean survival duration after surgery for the patients of AS and BS groups was 57.6 and 50.4 months respectively which was significantly longer than those patients of Nil group (MST: 26.4 months: p<0.001 respectively). Multivariate analysis revealed the addition of chemotherapy as a single prognostic factor of the patients. However, there was no significant difference of
November 2017
Abstracts
S2233
survival duration between the patients of AS and BS groups. Conclusion: Chemotherapy given both as adjuvant or neoadjuvant setting can provide a survival benefit for the patients with stage IIIa N2+ non-small cell lung cancer after surgery. No statistical difference was observed about the survival duration for these two groups of patients. Keywords: chemotherapy, NSCLC, Advanced NSCLS
Fig 1. Overall survival of pathological N2 according to type of resection.
P3.01-080 Overall Survival (OS) of Pathological N2 Non-Small Cell Lung Cancer (NSCLC) After Surgical Resection E. Bourdages-Pageau,1 A. Vieira,2 C. Labbé,2 P. Ugalde Figueroa3 1 Laval University, Quebec/QC/CA, 2Thoracic Surgery, Institut Universitaire de Cardiologie Et de Pneumologie de Québec (Iucpq), Québec/CA, 3Thoracic Surgery, Institut Universitaire de Cardiologie Et Pneumologie de Quebec, Quebec/QC/CA Background: Despite complete pre-operative staging, incidental N2 disease is still found during surgical resection of NSCLC. Proceeding with resection versus aborting the operation to treat with definitive chemotherapy and radiotherapy is controversial. The aim of the current study was to evaluate survival of pathological N2 disease after complete resection. Method: The Institut de Cardiologie et Pneumologie de Quebec Biobank was queried for all patients with pathological N2 NSCLC who underwent complete (R0) surgical resection either by lobectomy, bilobectomy or pneumonectomy between January 2000 and February 2017. Survival was examined using the Kaplan-Meier method with log rank analysis. Significance was set at p0.05. Result: We identified 224 eligible patients; 119 (53%) were male, mean age was 63±9, there were 143 (64%) adenocarcinoma and 60 (27%) squamous cell carcinoma. Regarding surgical modality, 156 (70%) patients underwent lobectomy or bilobectomy and 68 (30%) pneumonectomy. The 30-day mortality of the cohort was 3% (5 pneumonectomy and 2 lobectomy). During 17 years of follow-up, 142 (63%) patients died, including 87 (61%) in the lobectomy/bilobectomy group and 55 (39%) in the pneumonectomy group. Among all deaths, 105 (74%) were cancer-related. Median OS of the entire cohort was 2.6 y (CI 1.9-4.4). In the univariate analysis cox model, median OS was shorter for pneumonectomy than lobectomy/bilobectomy (2,1 years [1,6-2,6) vs 4,4 years [2,2-5,8]), HR 1.54 (CI 1.09 e 2.16, p¼0.01; figure 1). However, when only considering cancer-related deaths, the difference was not statistically significant (p¼0.95). Conclusion: In our institutional database study, median OS after surgical resection of N2 NSCLC was 2.6y. Pneumonectomy is indicated as cancer cure treatment however, major efforts should be made to decrease peri-operative morbidity and mortality.
P3.01-081 Overall Survival (OS) of Locally Advanced Non-Small Cell Lung Cancer (NSCLC) After Negative Invasive Mediastinal Staging E. Bourdages-Pageau,1 A. Vieira,2 C. Labbé,2 P. Ugalde Figueroa3 Laval University, Quebec/QC/CA, 2Thoracic Surgery, Institut Universitaire de Cardiologie Et de Pneumologie de Québec (Iucpq), Québec/CA, 3Thoracic Surgery, Institut Universitaire de Cardiologie Et Pneumologie de Quebec, Quebec/QC/CA
1
Background: According to current guidelines, invasive pre-operative staging should be performed with endoscopic ultrasound in NSCLC in suspected N2 disease. Due to its higher negative predictive value, in case of PET positive, CT enlarged mediastinal lymph nodes or central tumors, mediastinoscopy remains indicated when EBUS staging is negative. The aim of the current study was to evaluate OS of patients with locally advanced NSCLC who underwent surgical resection after negative EBUS and mediastinoscopy. Method: The Institut de Cardiologie et Pneumologie de Quebec Biobank was queried for all patients with high probability of N2 disease or central tumors with negative EBUS and mediastinoscopy that underwent complete surgical resection (R0) between March 2009 and February 2017. Survival was examined using the Kaplan-Meier method with log rank analysis. Significance was set at p0.05. Result: We identified 88 eligible patients (Table 1); 56 (64%) were male, mean age was 65±9 and 50% of the cases were adenocarcinoma. Regarding surgical modality, 1 (1%) patient underwent sublobar resection, 65 (74%) lobectomy or bilobectomy and 22 (25%) pneumonectomy. Among these, there were 11 (13%) pathological N2 cases. There was no 30-day mortality. During 8 years of follow-up, 30 patients died, including 20 (31%) in the lobectomy/ bilobectomy group compared to 9 (41%) in the pneumonectomy group. We then identified 16 (80%) cancer-related deaths in the lobectomy/bilobectomy and 7 (78%) in the pneumonectomy group. Median OS of the entire cohort was 5.7 years, with no difference between groups (HR 1.29, CI 0.58-2.87, p¼0.53). Conclusion: In our institutional database, patients locally advanced NSCLC had 13% incidence of pathological N2 disease and the OS was 5.7y. Our data supports surgical complete resection either by lobectomy or pneumonectomy in this group of patients with locally advanced disease. Keywords: mediastinal staging, pneumonectomy and lobectomy