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P0078 Percutaneous comprehensive cryoablation for metastatic oesophageal cancer after failure of radical surgery
Abstracts / 50 (2014) e1–e74
before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14–29 months (median, 18 months), and did not differ between patients with large tumours and those with small tumours (p = 0.6753). Interpretation: Cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma.
http://dx.doi.org/10.1016/j.ejca.2014.03.121
P0078 PERCUTANEOUS COMPREHENSIVE CRYOABLATION FOR METASTATIC OESOPHAGEAL CANCER AFTER FAILURE OF RADICAL SURGERY X. Jiongyuan *, N. Lizhi, M. Feng, L. Shupeng, L. Yin, L. Mengtian, Z. Jianying, Y. Fei, C. Jibing, L. Jialiang, X. Kecheng. Fuda Cancer Hospital, Jinan University School of Medicine, China Background: Oesophageal cancer is common in China. There is a lack of treatment strategies for metastatic oesophageal cancer (MEC) after radical surgery on the primary tumour. Cryoablation is an attractive option because tumour necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. Methods: One hundred and forty patients met the inclusion criteria between May 2003 and March 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. Overall survival (OS) was assessed according to therapeutic protocol, pathological type, treatment timing, and number of procedures. Findings: No severe complications occurred during or after cryoablation. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; p = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; p = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; p = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; p = 0.0172); and the OS for cryoimmunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; p = 0.0011). Interpretation: Comprehensive cryotherapy could have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation could be associated with a better prognosis.
http://dx.doi.org/10.1016/j.ejca.2014.03.122
P0079 ALLEVIATING THE PAIN OF UNRESECTABLE HEPATIC TUMOURS BY PERCUTANEOUS CRYOABLATION: EXPERIENCE IN 73 PATIENTS L. Xin’an *, Z. Jianying, N. Lizhi, Y. Fei, W. Xiaohua, C. Jibing, L. Jialiang, X. Kecheng. Fuda Cancer Hospital, Jinan University School of Medicine, China
e31
Background: Pain caused by liver tumours can be alleviated by cryoablation, but little is known about the analgesic effects and duration of pain alleviation. Methods: We retrospectively reviewed the changes in the severity of pain before and after percutaneous cryoablation of hepatic tumours. Each patient enrolled in this study had a single hepatic tumour; patients with large tumours (major diameter >5 cm) underwent transarterial chemoembolisation (TACE) first and then cryoablation. Severe abdominal pain that was not controlled with long-lasting oral analgesics was treated with opioid injections. Findings: In all 73 study patients, severe abdominal pain was gradually eased 5 days after cryosurgery, completely disappeared after 15 days, and did not recur for more than 8 weeks. There were no differences in analgesic effects in between patients with hepatocellular carcinomas and those with liver metastasis (p > 0.05). The patients were divided into four groups depending on their pain outcomes: (i) immediate relief (n = 6), severe abdominalgia was no longer present after cryosurgery; (ii) delayed relief (n = 11), severe abdominalgia disappeared gradually within 15 days after the cryosurgery; (iii) always pain-free (n = 39), severe abdominalgia was not present before or after treatment; and (iv) new pain (n = 17), abdominalgia developed after treatment and disappeared within 15 days. Interpretation: Percutaneous cryoablation of hepatic tumours caused short-term pain in some patients, but this pain disappeared within 15 days. Moreover, the pain-relieving effect of this treatment was sustained for at least 8 weeks, without severe side effects.
http://dx.doi.org/10.1016/j.ejca.2014.03.123
P0081 SRC INHIBITORS ACT THROUGH DIFFERENT MECHANISMS TO COOPERATE WITH EGFR OR MEK INHIBITORS IN NSCLC MODELS SENSITIVE OR RESISTANT TO ERLOTINIB L. Raimondo *, L. Formisano, R. Rosa, C. D’Amato, V. D’Amato, L. Nappi, R. Marciano, C. Di Mauro, A. Servetto, V. Damiano, B.M. Veneziani, S. De Placido, R. Bianco . University of Naples Federico II, Naples, Italy Background: The EGFR tyrosine kinase inhibitors gefitinib and erlotinib are first-line therapy for NSCLCs harbouring EGFR-activating mutations. The intrinsic and acquired resistance to these agents is a relevant clinical issue. Although Src tyrosine kinase has been involved in such resistance in preclinical models, clinical development of these agents has been so far limited. Methods: We used a panel of human NSCLC cell lines: PC9 and HCC827 (EGFR-activating mutation; highly sensitive to erlotinib), Calu3 (EGFR/Ras wild-type, wt; moderately sensitive), Calu3-ER (with acquired resistance), H1299 and A549 (Ras mutant; resistant), H1975 (EGFR T790M mutant; resistant). In these models, we tested three different Src inhibitors (saracatinib, dasatinib, and bosutinib), both in vitro and in vivo. Findings: NSCLC cell lines showed different activation of EGFRdependent and Src-dependent pathways and variable sensitivity to Src inhibitors. A kinase assay demonstrated that all the compounds are able to directly inhibit EGFR tyrosine kinase variants. In cell lysates only saracatinib and bosutinib efficiently reduced EGFR activation, while dasatinib was the more effective agent in inhibiting Src tyrosine kinase. Consistently, in EGFR-activating mutant, erlotinib sensitive cells, saracatinib and bosutinib showed anti-proliferative effects related to simultaneous EGFR/Src inhibition. In EGFR wt/Ras mutant cells Src inhibition by dasatinib interfered with cell
before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14–29 months (median, 18 months), and did not differ between patients with large tumours and those with small tumours (p = 0.6753). Interpretation: Cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma.
http://dx.doi.org/10.1016/j.ejca.2014.03.121
P0078 PERCUTANEOUS COMPREHENSIVE CRYOABLATION FOR METASTATIC OESOPHAGEAL CANCER AFTER FAILURE OF RADICAL SURGERY X. Jiongyuan *, N. Lizhi, M. Feng, L. Shupeng, L. Yin, L. Mengtian, Z. Jianying, Y. Fei, C. Jibing, L. Jialiang, X. Kecheng. Fuda Cancer Hospital, Jinan University School of Medicine, China Background: Oesophageal cancer is common in China. There is a lack of treatment strategies for metastatic oesophageal cancer (MEC) after radical surgery on the primary tumour. Cryoablation is an attractive option because tumour necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. Methods: One hundred and forty patients met the inclusion criteria between May 2003 and March 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. Overall survival (OS) was assessed according to therapeutic protocol, pathological type, treatment timing, and number of procedures. Findings: No severe complications occurred during or after cryoablation. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; p = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; p = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; p = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; p = 0.0172); and the OS for cryoimmunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; p = 0.0011). Interpretation: Comprehensive cryotherapy could have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation could be associated with a better prognosis.
http://dx.doi.org/10.1016/j.ejca.2014.03.122
P0079 ALLEVIATING THE PAIN OF UNRESECTABLE HEPATIC TUMOURS BY PERCUTANEOUS CRYOABLATION: EXPERIENCE IN 73 PATIENTS L. Xin’an *, Z. Jianying, N. Lizhi, Y. Fei, W. Xiaohua, C. Jibing, L. Jialiang, X. Kecheng. Fuda Cancer Hospital, Jinan University School of Medicine, China
e31
Background: Pain caused by liver tumours can be alleviated by cryoablation, but little is known about the analgesic effects and duration of pain alleviation. Methods: We retrospectively reviewed the changes in the severity of pain before and after percutaneous cryoablation of hepatic tumours. Each patient enrolled in this study had a single hepatic tumour; patients with large tumours (major diameter >5 cm) underwent transarterial chemoembolisation (TACE) first and then cryoablation. Severe abdominal pain that was not controlled with long-lasting oral analgesics was treated with opioid injections. Findings: In all 73 study patients, severe abdominal pain was gradually eased 5 days after cryosurgery, completely disappeared after 15 days, and did not recur for more than 8 weeks. There were no differences in analgesic effects in between patients with hepatocellular carcinomas and those with liver metastasis (p > 0.05). The patients were divided into four groups depending on their pain outcomes: (i) immediate relief (n = 6), severe abdominalgia was no longer present after cryosurgery; (ii) delayed relief (n = 11), severe abdominalgia disappeared gradually within 15 days after the cryosurgery; (iii) always pain-free (n = 39), severe abdominalgia was not present before or after treatment; and (iv) new pain (n = 17), abdominalgia developed after treatment and disappeared within 15 days. Interpretation: Percutaneous cryoablation of hepatic tumours caused short-term pain in some patients, but this pain disappeared within 15 days. Moreover, the pain-relieving effect of this treatment was sustained for at least 8 weeks, without severe side effects.
http://dx.doi.org/10.1016/j.ejca.2014.03.123
P0081 SRC INHIBITORS ACT THROUGH DIFFERENT MECHANISMS TO COOPERATE WITH EGFR OR MEK INHIBITORS IN NSCLC MODELS SENSITIVE OR RESISTANT TO ERLOTINIB L. Raimondo *, L. Formisano, R. Rosa, C. D’Amato, V. D’Amato, L. Nappi, R. Marciano, C. Di Mauro, A. Servetto, V. Damiano, B.M. Veneziani, S. De Placido, R. Bianco . University of Naples Federico II, Naples, Italy Background: The EGFR tyrosine kinase inhibitors gefitinib and erlotinib are first-line therapy for NSCLCs harbouring EGFR-activating mutations. The intrinsic and acquired resistance to these agents is a relevant clinical issue. Although Src tyrosine kinase has been involved in such resistance in preclinical models, clinical development of these agents has been so far limited. Methods: We used a panel of human NSCLC cell lines: PC9 and HCC827 (EGFR-activating mutation; highly sensitive to erlotinib), Calu3 (EGFR/Ras wild-type, wt; moderately sensitive), Calu3-ER (with acquired resistance), H1299 and A549 (Ras mutant; resistant), H1975 (EGFR T790M mutant; resistant). In these models, we tested three different Src inhibitors (saracatinib, dasatinib, and bosutinib), both in vitro and in vivo. Findings: NSCLC cell lines showed different activation of EGFRdependent and Src-dependent pathways and variable sensitivity to Src inhibitors. A kinase assay demonstrated that all the compounds are able to directly inhibit EGFR tyrosine kinase variants. In cell lysates only saracatinib and bosutinib efficiently reduced EGFR activation, while dasatinib was the more effective agent in inhibiting Src tyrosine kinase. Consistently, in EGFR-activating mutant, erlotinib sensitive cells, saracatinib and bosutinib showed anti-proliferative effects related to simultaneous EGFR/Src inhibition. In EGFR wt/Ras mutant cells Src inhibition by dasatinib interfered with cell