- Email: [email protected]
P0103 Results of breast conserving surgery in locally advanced breast cancer following neoadjuvant chemotherapy
Abstracts / 50 (2014) e1–e74
margin-positive resections after immediate reconstruction of chest wall with good cosmetic outcome and less donor site morbidity.
http://dx.doi.org/10.1016/j.ejca.2014.03.140
P0097 ALK REARRANGEMENTS IN TURKISH PATIENTS WITH LUNG ADENOCARCINOMA _ Atli a,*, M.C. Yakicier a, A. Akin b . a Acibadem University E.I. Molecular Biology and Genetic Department, Turkey, b Acibadem Genetic Diagnostic Center, Turkey Background: We aimed to establish the frequency of ALK translocation in lung adenocarcinomas at a population level. Methods: Between 2011 and 2013, 157 paraffin embedded tumour tissue samples were collected by our hospitals. Forty patients from this group were also scanned for EGFR mutations. FISH technique was used on paraffin embedded tissues, which were cut 4 microns thick. Vysis ALK Breakapart FISH probe kit was used to detect rearrangement of ALK gene. Findings: Twenty patients (12.7%) were positive for ALK rearrangement. ALK-positive patients were younger than ALK-negative patients. Interpretation: Our study is the first to investigate the ALK status of lung cancers in Turkish patients.
http://dx.doi.org/10.1016/j.ejca.2014.03.141
e37
Istanbul, Turkey, b Near East University, Genetics and Cancer Diagnosis Research Center, Cyprus, c Eskisehir Osmangazi University Medical School, Turkey Background: We aimed to assess the relationship between the methylation of the tumour suppressor gene RARb and response to treatment and survival in patients with primary glioblastoma. Methods: Forty patients were involved. RARb promoter methylation was studied with MS-HRM. Findings: Methylation of RARb was noted in 24 (60%) of the 40 patients with primary glioblastoma multiforme. Three samples were 25% methylated, five were 50% methyl, four were 75% methylated, and 12 were 100%. Mean survival time of the patients with methylated RARb was 19 months, compared with 15 months for those not methylated. Twenty-eight patients received treatment, the remaining 12 cases had no data regarding treatment. RARb patients receiving and not receiving treatment according to the methylation patterns were compared in terms of survival. Patients who received treatment with chemotherapy and radiotherapy survived for 25 months. Patients who received radiotherapy alone or no treatment protocol survived for 15–20 months. Interpretation: Our findings should be replicated in larger series.
http://dx.doi.org/10.1016/j.ejca.2014.03.144
P0103 RESULTS OF BREAST CONSERVING SURGERY IN LOCALLY ADVANCED BREAST CANCER FOLLOWING NEOADJUVANT CHEMOTHERAPY S. Agrawal *, S. Chattorjee, I. Ghosh, R. Ahmed. Tata Medical Center, India
P0098 IDH2 MUTATIONS IN TURKISH PATIENTS WITH PRIMARY GLIOBLASTOMA _ Atli a,*, R. O ¨ zkut b, S. Artan c, A. Arslantasß c, M. O ¨ zdemir c . E.I. Acibadem University Molecular Biology and Genetics Department, Istanbul, Turkey, b Near East University, Genetics and Cancer Diagnosis Research Center, Cyprus, c Eskisehir Osmangazi University Medical School, Turkey a
Background: We aimed to establish the frequency of IDH2 mutations in primary glioblastoma at a population level. Methods: We screened primary glioblastoma in a population-based study for IDH2 mutations and correlated them with clinical data. Findings: No IDH2 mutations were detected in tumour samples. Interpretation: Since the analysed tumours were primary glioblastoma, our data regarding IDH2 mutations was in agreement with the literature.
http://dx.doi.org/10.1016/j.ejca.2014.03.142
P0100 RARB METHYLATION IN PRIMARY GLIOBLASTOMA
TURKISH
PATIENTS
WITH
_ Atli a,*, R. O ¨ zkut b, S. Artan c, A. Arslantasß c, M. O ¨ zdemir c . E.I. Acibadem University Molecular Biology and Genetics Department,
a
Background: Locally advanced breast cancer (LABC) includes patients with large tumours, extensive regional lymph node involvement, and direct involvement of the skin or underlying chest wall. Neoadjuvant chemotherapy followed by surgery, with adjuvant radiotherapy and hormonal therapy, has become the standard of care and a valuable strategy in the multimodal management of LABC. Methods: This single institution, retrospective cohort study was done at Tata Medical Center for patients operated after neoadjuvant chemotherapy for LABC between November 2012 and August 2013. Eighty-nine women (30% of total breast surgeries) had undergone surgery after neoadjuvant chemotherapy during this period. Anthracycline-based chemotherapy regimens (FECx6 or FEC-Tx6) were always completed before surgery. All patients had adjuvant radiotherapy, with endocrine therapy if appropriate. Median follow up is 9 months. Findings: Twenty-seven women requested breast conservation but at presentation had tumours too large. Conservation was possible in 24 women (three with volume replacement). Three others had mastectomy (two with immediate reconstruction). One had a second excision for close margins. Sixty-two women had fungating, inoperable or multi-quadrant tumours, necessitating mastectomy. Overall 26% of patients had a complete pathological response (23% in mastectomy and 37.5% in breast conserving surgery groups, chi-square 1.85, p = 0.17). Of the mastectomy patients, 18% had early lymphoedema. No lymphoedema was seen after breast conserving surgery (chi-square 4.1, p = 0.04). Local recurrence occurred in 6% of women following mastectomy, all in patients presenting with T4 disease. No local recurrence was seen after breast conserving surgery.
e38
Abstracts / 50 (2014) e1–e74
Interpretation: Neoadjuvant chemotherapy converts patients initially ineligible for breast conserving surgery into candidates for such surgery. We believe that the key to the successful breast conserving surgery after neoadjuvant chemotherapy is careful patient selection and coordination among specialties.
http://dx.doi.org/10.1016/j.ejca.2014.03.147
P0104 MDM2 AND P53 CODON 72 POLYMORPHISMS IN ACUTE MYELOID LEUKAEMIA N.M. El-Danasouri a, S.H. Ragab b, M.A. Rasheed b, Z.A. El-Sadaany a, S.N. Abd El-Fattah b,*. a Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Egypt, b Department of Clinical and Chemical Pathology, National Research Centre, Egypt
inhibit the growth and tumorigenicity of HeLa human cervical cancer cells and U87-MG human glioblastoma multiforme cells. However, the antitumour effects of hTERTC27 in hepatoma and its underlying mechanisms are unclear. Methods: In the current study, the therapeutic effect of hTERTC27, mediated by recombinant adenovirus, in hepatocellular carcinoma was explored in vitro and in vivo to investigate the possible mechanisms. Findings: Recombinant adenovirus carrying hTERTC27 (rAdvhTERTC27) effectively inhibited the growth and induced apoptosis of Hepa 1–6 cell lines. Dendritic cells transduced with rAdv-hTERTC27 were highly effective at inducing antigen-specific T cell proliferation and increasing the activated cytotoxicity of T cells against Hepa 1–6 cells. Hepatocellular carcinoma was inhibited significantly when a single dose of 5 107 pfu rAdv-hTERTC27 was administered intravenously. Interpretation: Our results suggest that rAdv-hTERTC27 may serve as a reagent for intravenous administration when combined with telomerase-based gene therapy and immunotherapy for cancer.
http://dx.doi.org/10.1016/j.ejca.2014.03.149
Background: Acute myeloid leukaemia (AML) is a heterogenous disease with numerous genetic abnormalities corresponding to a variety of subtypes. P53 is a principle mediator of multiple cellular functions including cell cycle arrest, senescence, and apoptosis in response to cellular stresses. The activity of P53 may either be inactivated or attenuated in a vast majority of human cancers through mutations in the P53 gene or aberrant expression of proteins acting in the P53 tumour suppression pathway, such as its key cellular regulator MDM2. Single nucleotide polymorphism (SNP) at codon 72 of the P53 gene (A-G exchange) alters the primary structure of the P53 protein. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the promoter of the MDM2 gene which increase the expression of MDM2, thereby impairing the tumour suppressor activity of P53. We aimed at defining the role of MDM2 SNP309 and P53 codon 72 polymorphisms in the risk of AML. Methods: Genotyping for MDM2 SNP309 and P53 codon 72 polymorphisms was done by AS-PCR and PCR-RFLP techniques respectively, for 50 de-novo adult AML patients and 50 healthy age and sex matched controls. Findings: We found a borderline significant statistical difference between cases and controls regarding combined MDM2 T/G and P53 genotypes. There was no significant correlation between either MDM2 SNP309 or P53 codon 72 polymorphisms alone and the risk of AML. MDM2 variant genotypes were significantly associated with lower age of onset of AML and lower haemoglobin level while P53 variants were significantly associated with lower CD117 expression. Interpretation: An interactive effect between MDM2 SNP309 and P53 codon 72 polymorphisms may increase the risk of AML.
P0106 ANTITUMOUR IMMUNITY AGAINST MURINE GLIOMAS USING DENDRITIC CELLS TRANSDUCED WITH HTERTC27RECOMBINANT ADENOVIRUS L. He *, H. Gong, X. Li, Y. Wang, Y. Li, Y. Peng. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China Background: hTERTC27, a 27-kDa hTERT C-terminal polypeptide has been shown to cause hTERT-positive HeLa cell apoptosis and inhibit the growth of mouse melanoma. hTERTC27 has been associated with telomere dysfunction, regulation of gene-regulated apoptosis, the cell cycle, and activation of natural killer cells, but its mechanism of action is not fully understood. Methods: We examined the effect of hTERTC27 transduced dendritic cells both in vitro and in vivo. Findings: Dendritic cells transduced with hTERTC27 increased T-cell proliferation, and augmented the concentration of interleukin 2 and interferon-c in the supernatants of T cells. They also induced antigen-specific cytotoxic T lymphocytes against glioma cells in vitro. Moreover, hTERTC27 gene-transduced dendritic cells exhibited potent cytotoxicity to glioma cells in vivo. Interpretation: These data suggest that hTERTC27 gene-transduced dendritic cells can efficiently enhance immunity against gliomas in vitro and in vivo.
http://dx.doi.org/10.1016/j.ejca.2014.03.148 http://dx.doi.org/10.1016/j.ejca.2014.03.150
P0105 INHIBITION OF HEPATOCELLULAR CARCINOMA GROWTH BY ADENOVIRUS-MEDIATED EXPRESSION OF HUMAN TELOMERASE REVERSE TRANSCRIPTASE COOH-27 TERMINAL POLYPEPTIDE IN MICE L. He *, H. Gong, X. Li, Y. Wang, Y. Li, Y. Peng. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China Background: A 27-kDa C-terminal fragment of human telomerase reverse transcriptase, hTERTC27, has previously been reported to
P0107 DOSE TO DYSPHAGIA ASPIRATION-RELATED STRUCTURES AND ITS EFFECT ON SWALLOWING: COMPARISON OF 3D CRT AND IMRT PLANS C.G. Prameela a,*, R. Ravind a,b,*, M. Haridas Nair a, P.S. Renil Mon b, V.S. Sheejamol c, D. Makuny a . a Department of Radiation Oncology, Amrita Institute of Medical Sciences & Research Centre, Kochi, Kerala, India, b Department of Medical Physics & Radiation Safety, Amrita Institute of Medical Sciences & Research Centre, Kochi,
margin-positive resections after immediate reconstruction of chest wall with good cosmetic outcome and less donor site morbidity.
http://dx.doi.org/10.1016/j.ejca.2014.03.140
P0097 ALK REARRANGEMENTS IN TURKISH PATIENTS WITH LUNG ADENOCARCINOMA _ Atli a,*, M.C. Yakicier a, A. Akin b . a Acibadem University E.I. Molecular Biology and Genetic Department, Turkey, b Acibadem Genetic Diagnostic Center, Turkey Background: We aimed to establish the frequency of ALK translocation in lung adenocarcinomas at a population level. Methods: Between 2011 and 2013, 157 paraffin embedded tumour tissue samples were collected by our hospitals. Forty patients from this group were also scanned for EGFR mutations. FISH technique was used on paraffin embedded tissues, which were cut 4 microns thick. Vysis ALK Breakapart FISH probe kit was used to detect rearrangement of ALK gene. Findings: Twenty patients (12.7%) were positive for ALK rearrangement. ALK-positive patients were younger than ALK-negative patients. Interpretation: Our study is the first to investigate the ALK status of lung cancers in Turkish patients.
http://dx.doi.org/10.1016/j.ejca.2014.03.141
e37
Istanbul, Turkey, b Near East University, Genetics and Cancer Diagnosis Research Center, Cyprus, c Eskisehir Osmangazi University Medical School, Turkey Background: We aimed to assess the relationship between the methylation of the tumour suppressor gene RARb and response to treatment and survival in patients with primary glioblastoma. Methods: Forty patients were involved. RARb promoter methylation was studied with MS-HRM. Findings: Methylation of RARb was noted in 24 (60%) of the 40 patients with primary glioblastoma multiforme. Three samples were 25% methylated, five were 50% methyl, four were 75% methylated, and 12 were 100%. Mean survival time of the patients with methylated RARb was 19 months, compared with 15 months for those not methylated. Twenty-eight patients received treatment, the remaining 12 cases had no data regarding treatment. RARb patients receiving and not receiving treatment according to the methylation patterns were compared in terms of survival. Patients who received treatment with chemotherapy and radiotherapy survived for 25 months. Patients who received radiotherapy alone or no treatment protocol survived for 15–20 months. Interpretation: Our findings should be replicated in larger series.
http://dx.doi.org/10.1016/j.ejca.2014.03.144
P0103 RESULTS OF BREAST CONSERVING SURGERY IN LOCALLY ADVANCED BREAST CANCER FOLLOWING NEOADJUVANT CHEMOTHERAPY S. Agrawal *, S. Chattorjee, I. Ghosh, R. Ahmed. Tata Medical Center, India
P0098 IDH2 MUTATIONS IN TURKISH PATIENTS WITH PRIMARY GLIOBLASTOMA _ Atli a,*, R. O ¨ zkut b, S. Artan c, A. Arslantasß c, M. O ¨ zdemir c . E.I. Acibadem University Molecular Biology and Genetics Department, Istanbul, Turkey, b Near East University, Genetics and Cancer Diagnosis Research Center, Cyprus, c Eskisehir Osmangazi University Medical School, Turkey a
Background: We aimed to establish the frequency of IDH2 mutations in primary glioblastoma at a population level. Methods: We screened primary glioblastoma in a population-based study for IDH2 mutations and correlated them with clinical data. Findings: No IDH2 mutations were detected in tumour samples. Interpretation: Since the analysed tumours were primary glioblastoma, our data regarding IDH2 mutations was in agreement with the literature.
http://dx.doi.org/10.1016/j.ejca.2014.03.142
P0100 RARB METHYLATION IN PRIMARY GLIOBLASTOMA
TURKISH
PATIENTS
WITH
_ Atli a,*, R. O ¨ zkut b, S. Artan c, A. Arslantasß c, M. O ¨ zdemir c . E.I. Acibadem University Molecular Biology and Genetics Department,
a
Background: Locally advanced breast cancer (LABC) includes patients with large tumours, extensive regional lymph node involvement, and direct involvement of the skin or underlying chest wall. Neoadjuvant chemotherapy followed by surgery, with adjuvant radiotherapy and hormonal therapy, has become the standard of care and a valuable strategy in the multimodal management of LABC. Methods: This single institution, retrospective cohort study was done at Tata Medical Center for patients operated after neoadjuvant chemotherapy for LABC between November 2012 and August 2013. Eighty-nine women (30% of total breast surgeries) had undergone surgery after neoadjuvant chemotherapy during this period. Anthracycline-based chemotherapy regimens (FECx6 or FEC-Tx6) were always completed before surgery. All patients had adjuvant radiotherapy, with endocrine therapy if appropriate. Median follow up is 9 months. Findings: Twenty-seven women requested breast conservation but at presentation had tumours too large. Conservation was possible in 24 women (three with volume replacement). Three others had mastectomy (two with immediate reconstruction). One had a second excision for close margins. Sixty-two women had fungating, inoperable or multi-quadrant tumours, necessitating mastectomy. Overall 26% of patients had a complete pathological response (23% in mastectomy and 37.5% in breast conserving surgery groups, chi-square 1.85, p = 0.17). Of the mastectomy patients, 18% had early lymphoedema. No lymphoedema was seen after breast conserving surgery (chi-square 4.1, p = 0.04). Local recurrence occurred in 6% of women following mastectomy, all in patients presenting with T4 disease. No local recurrence was seen after breast conserving surgery.
e38
Abstracts / 50 (2014) e1–e74
Interpretation: Neoadjuvant chemotherapy converts patients initially ineligible for breast conserving surgery into candidates for such surgery. We believe that the key to the successful breast conserving surgery after neoadjuvant chemotherapy is careful patient selection and coordination among specialties.
http://dx.doi.org/10.1016/j.ejca.2014.03.147
P0104 MDM2 AND P53 CODON 72 POLYMORPHISMS IN ACUTE MYELOID LEUKAEMIA N.M. El-Danasouri a, S.H. Ragab b, M.A. Rasheed b, Z.A. El-Sadaany a, S.N. Abd El-Fattah b,*. a Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Egypt, b Department of Clinical and Chemical Pathology, National Research Centre, Egypt
inhibit the growth and tumorigenicity of HeLa human cervical cancer cells and U87-MG human glioblastoma multiforme cells. However, the antitumour effects of hTERTC27 in hepatoma and its underlying mechanisms are unclear. Methods: In the current study, the therapeutic effect of hTERTC27, mediated by recombinant adenovirus, in hepatocellular carcinoma was explored in vitro and in vivo to investigate the possible mechanisms. Findings: Recombinant adenovirus carrying hTERTC27 (rAdvhTERTC27) effectively inhibited the growth and induced apoptosis of Hepa 1–6 cell lines. Dendritic cells transduced with rAdv-hTERTC27 were highly effective at inducing antigen-specific T cell proliferation and increasing the activated cytotoxicity of T cells against Hepa 1–6 cells. Hepatocellular carcinoma was inhibited significantly when a single dose of 5 107 pfu rAdv-hTERTC27 was administered intravenously. Interpretation: Our results suggest that rAdv-hTERTC27 may serve as a reagent for intravenous administration when combined with telomerase-based gene therapy and immunotherapy for cancer.
http://dx.doi.org/10.1016/j.ejca.2014.03.149
Background: Acute myeloid leukaemia (AML) is a heterogenous disease with numerous genetic abnormalities corresponding to a variety of subtypes. P53 is a principle mediator of multiple cellular functions including cell cycle arrest, senescence, and apoptosis in response to cellular stresses. The activity of P53 may either be inactivated or attenuated in a vast majority of human cancers through mutations in the P53 gene or aberrant expression of proteins acting in the P53 tumour suppression pathway, such as its key cellular regulator MDM2. Single nucleotide polymorphism (SNP) at codon 72 of the P53 gene (A-G exchange) alters the primary structure of the P53 protein. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the promoter of the MDM2 gene which increase the expression of MDM2, thereby impairing the tumour suppressor activity of P53. We aimed at defining the role of MDM2 SNP309 and P53 codon 72 polymorphisms in the risk of AML. Methods: Genotyping for MDM2 SNP309 and P53 codon 72 polymorphisms was done by AS-PCR and PCR-RFLP techniques respectively, for 50 de-novo adult AML patients and 50 healthy age and sex matched controls. Findings: We found a borderline significant statistical difference between cases and controls regarding combined MDM2 T/G and P53 genotypes. There was no significant correlation between either MDM2 SNP309 or P53 codon 72 polymorphisms alone and the risk of AML. MDM2 variant genotypes were significantly associated with lower age of onset of AML and lower haemoglobin level while P53 variants were significantly associated with lower CD117 expression. Interpretation: An interactive effect between MDM2 SNP309 and P53 codon 72 polymorphisms may increase the risk of AML.
P0106 ANTITUMOUR IMMUNITY AGAINST MURINE GLIOMAS USING DENDRITIC CELLS TRANSDUCED WITH HTERTC27RECOMBINANT ADENOVIRUS L. He *, H. Gong, X. Li, Y. Wang, Y. Li, Y. Peng. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China Background: hTERTC27, a 27-kDa hTERT C-terminal polypeptide has been shown to cause hTERT-positive HeLa cell apoptosis and inhibit the growth of mouse melanoma. hTERTC27 has been associated with telomere dysfunction, regulation of gene-regulated apoptosis, the cell cycle, and activation of natural killer cells, but its mechanism of action is not fully understood. Methods: We examined the effect of hTERTC27 transduced dendritic cells both in vitro and in vivo. Findings: Dendritic cells transduced with hTERTC27 increased T-cell proliferation, and augmented the concentration of interleukin 2 and interferon-c in the supernatants of T cells. They also induced antigen-specific cytotoxic T lymphocytes against glioma cells in vitro. Moreover, hTERTC27 gene-transduced dendritic cells exhibited potent cytotoxicity to glioma cells in vivo. Interpretation: These data suggest that hTERTC27 gene-transduced dendritic cells can efficiently enhance immunity against gliomas in vitro and in vivo.
http://dx.doi.org/10.1016/j.ejca.2014.03.148 http://dx.doi.org/10.1016/j.ejca.2014.03.150
P0105 INHIBITION OF HEPATOCELLULAR CARCINOMA GROWTH BY ADENOVIRUS-MEDIATED EXPRESSION OF HUMAN TELOMERASE REVERSE TRANSCRIPTASE COOH-27 TERMINAL POLYPEPTIDE IN MICE L. He *, H. Gong, X. Li, Y. Wang, Y. Li, Y. Peng. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China Background: A 27-kDa C-terminal fragment of human telomerase reverse transcriptase, hTERTC27, has previously been reported to
P0107 DOSE TO DYSPHAGIA ASPIRATION-RELATED STRUCTURES AND ITS EFFECT ON SWALLOWING: COMPARISON OF 3D CRT AND IMRT PLANS C.G. Prameela a,*, R. Ravind a,b,*, M. Haridas Nair a, P.S. Renil Mon b, V.S. Sheejamol c, D. Makuny a . a Department of Radiation Oncology, Amrita Institute of Medical Sciences & Research Centre, Kochi, Kerala, India, b Department of Medical Physics & Radiation Safety, Amrita Institute of Medical Sciences & Research Centre, Kochi,