- Email: [email protected]
P0226 Patterns of recurrence in locally advanced squamous cell carcinomas of the head and neck after three-dimensional conformal radiotherapy: An institutional experience
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Abstracts / 50 (2014) e1–e74
CYP3A5*3 (rs776746) polymorphisms by polymerase chain reaction– restriction fragment-length polymorphisms (PCR–RFLP). Logistic regression analysis was done to calculate risk association using EpiInfo 7.0 software. Findings: The distribution of CYP3A5*3 genotype was 41.5% (GG), 37.7% (GA), and 20.8% (AA) among the IM-resistant group, compared with 45.8% (GG), 33.3% (GA), and 20.9% (AA) among the IM-good-response group. There was no significant difference in genotype frequencies between the two groups (p = 0.91). On evaluating the risk of IM resistance, the frequencies of homozygous TT genotype and heterozygous TC variant of CYP3A4*18 were insignificantly associated with IM response (p = 0.25). Odds ratio was 0.34 (95% confidence interval [CI] 0.062–1.827, p = 0.19) for the CYP3A4*18 heterozygous variant, 1.25 (95% CI 0.516–3.026, p = 0.69) for the CYP3A5*3 heterozygous variant, and 1.10 (95% CI 0.389–3.114, p = 0.86) for the CYP3A5*3 homozygous variant. Interpretation: Our preliminary results suggest a lack of association between CYP3A4*18 and CYP3A5*3 gene polymorphisms and IM resistance. This study is being continued with a larger number of patients.
http://dx.doi.org/10.1016/j.ejca.2014.03.267
P0224 A NOVEL, SMALL MOLECULE INHIBITOR, MSU-1001, IN ANDROGEN-SENSITIVE PROSTATE CANCER CELL LINES P.K. Bhavar a,*, M.R. Yadav a, S.S. Dinavahi b, S. Nyayapathy b. Department of Pharmacy, M.S. University of Baroda, Gujarat, India, b Biological Research Lab, Incozen Therapeutics, Andrapradesh, India a
Introduction: Prostate cancer is one of the leading causes of cancerrelated death in men worldwide. Current treatment options are limited to traditional chemotherapy, surgery, radiation, or hormone therapy, which often have unwanted side effects. There is a need to develop safer molecules that attenuate tumour progression without adversely affecting the overall quality of life. We report the in vitro activity of a novel, synthetic, small molecule, with potential to be a lead candidate for the treatment of prostate cancer. Methods: A library of novel small molecule inhibitors was developed through rational drug design. A pyrrolo-pyrimidine derivative (MSU-1001) was identified as a potential lead molecule. Prostate and colon cancer cell lines (LNCap, HT-29, and HCT-8) were obtained from the American Type Culture Collection (ATCC). Cells were incubated with various concentrations of MSU-1001 for 72 h. Growth inhibition was determined colorimetrically on a plate-reader using a 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Findings: Colon cancer cell lines HCT-8 and HT-29 were used in conjunction with the androgen-sensitive human prostate adenocarcinoma cell line, LNCaP, to investigate the specificity of MSU-1001 on tumour type. Among the library of compounds tested, MSU-1001 was pursued based on its anti-proliferative activity in LNCaP cells. Addition of MSU-1001 to LNCaP cells resulted in a dose-dependent inhibition of proliferation (GI50 = 161 nM) with a near-complete inhibition of cell growth noted at 10 lM. By contrast, GI50 of gemcitabine was more than 6-fold higher (GI50 = 1.21 lM) in LNCaP cells. Additionally, GI50 of MSU-1001 in HCT-8 and HT-29 was 1.8 and 8.7 lM, respectively, indicating relative specificity of MSU-1001 against prostate cancer. Interpretation: These data show the therapeutic potential of MSU-1001 in prostate cancer. Combination studies of MSU-1001 with
testosterone, 17b-estradiol, and dehydroepiandro-stenone in androgen-sensitive and insensitive prostate cancer cell lines are currently ongoing.
http://dx.doi.org/10.1016/j.ejca.2014.03.268
P0225 TELEMEDICINE: A NOVEL APPROACH OF BRINGING ONCOLOGY CARE CLOSER TO THE PATIENT D.M. Poprawski *, J. Adams, A. Bassal. Country Health South Australia Local Health Network (CHSALHN), Elizabeth Vale, SA, Australia Background: In Australia, long distances have motivated oncologists to try innovations in the provision of oncology care to improve cost efficiency, access, and compliance. This study aimed to demonstrate the use of telemedicine, a novel approach of bringing oncology care to regional centres, and its applicability across Asia and Oceania. Methods: A retrospective review of telemedicine clinic use was conducted for two South Australian regional sites (Whyalla and Mount Gambier) over a 12-month period. Findings: Between February 2013 and January 2014, 380 patients were reviewed in oncology telemedicine clinics (n = 152 in Whyalla, n = 228 in Mount Gambier). The average number of patients reviewed per month was 31 (n = 12, n = 19). As oncologists grew comfortable with the consultation technique, the types of consultations conducted by telemedicine were expanded. Numbers by consultation type were: pre-chemotherapy review, n = 285 (n = 135, n = 150); restaging, n = 39 (n = 15, n = 24); and first consultation, n = 6 (n = 2, n = 4). Both men and women were reviewed, age range was 24–87 years, and ethnicities included Indigenous, Australian, European, and Asian. A teleconferencing unit was used in the regional clinic and a computermounted camera at the oncologist’s clinic. The costs to run a telemedicine clinic will be compared to travel costs in a metropolitan-based approach. Interpretation: Telemedicine allows specialists to review patients on a regular basis during chemotherapy, without the need for travel to a major metropolitan centre. Uniformity and simplicity of approach makes telemedicine user-friendly and cost effective for patients and health services. Telemedicine provides a novel technique for safe and efficient oncology care closer to the patient’s home. The technique has clear savings by minimising travel and burden on metropolitan clinic budgets. This approach can be easily adapted to most countries in Asia and Oceania.
http://dx.doi.org/10.1016/j.ejca.2014.03.269
P0226 PATTERNS OF RECURRENCE IN LOCALLY ADVANCED SQUAMOUS CELL CARCINOMAS OF THE HEAD AND NECK AFTER THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY: AN INSTITUTIONAL EXPERIENCE A. Singh *, D.J. Fernandes, M.S. Vidyasagar, S.A. Reddy. Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital, Kasturba Medical College, Manipal, India
Abstracts / 50 (2014) e1–e74
Background: Loco-regional recurrences continue to plague head and neck cancers, even with combined modality treatment. We report patterns of loco-regional recurrence after three-dimensional (3D) conformal radiotherapy among patients with locally advanced (non-nasopharyngeal) head and neck squamous cell cancers. Methods: From 2009 to 2012, 263 patients with stage III–IV head and neck squamous cell carcinoma received treatment at our institute with radical external beam radiotherapy with or without chemotherapy. Patients who had surgical resection of primary tumour or nodal site were excluded. Sites of loco-regional relapses were compared and correlated with radiotherapy treatment plans by the radiation oncologist and medical physics team. Findings: Median follow-up was 38 months (range 3–62). Median patient age was 52 years. After a mean follow-up of 21 months (range 0–44), there were 42 patients with loco-regional failure. The median time to failure among these patients was 12.5 months (range 3–17). Of the 42 cases, 20 failed locally, 17 had regional failure, and five had simultaneous loco-regional failure. 38 patients had in-field recurrence, three had simultaneous in-field and out-of-field recurrence, and one patient had marginal recurrence. Interpretation: In this study, the predominant pattern of recurrence after 3D conformal radiotherapy was in-field. Sites of primary gross disease and nodal levels initially involved were the most common sites of recurrence. Further studies on radio-resistant tumour populations are needed, to enhance early identification and appropriate treatment intensification.
http://dx.doi.org/10.1016/j.ejca.2014.03.270
P0227 UTILITY OF PRE-TREATMENT SERUM AMPHIREGULIN IN COLORECTAL CARCINOMA C. Chayangsu a,*, P. Kanjanasilp b, S. Malakorn b, C. Sahakitrungruang b, S. Tanasanvimon a, P. Sitthideatphaiboon a, V. Sriuranpong a. a Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, b Division of Colorectal Surgery, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Amphiregulin (AREG) is an EGFR ligand that plays an important role in tumour progression and metastasis. Upregulation of AREG in colon cancer tissue has been correlated with liver metastasis. We investigated the correlation of serum AREG in colorectal cancer with clinico-pathological parameters. Methods: Colorectal cancer patients who received treatment at our institute from September to December 2013 were enrolled. We collected and stored baseline serum before the start of any therapy. Serum AREG was measured by ELISA using Human Amphiregulin DuoSet (R & D Systems, Minneapolis, MN). The correlation between independent clinico-pathological characteristics and serum AREG was analysed. Findings: 40 patients were enrolled and included in the analysis: 25 patients with stage I–III disease and 15 patients with advanced stage disease. In the advanced disease group, the mean level of serum AREG was 65.12 pg/mL (±89.49), which was higher than in the localised disease group (23.68 pg/mL [±37.89], p = 0.11). Serum AREG higher than 40 pg/mL significantly correlated with depth of tumour invasion (pT4) and distant metastases (M), and there was a trend toward association with lymphovascular invasion and perineural invasion.
e73
Interpretation: Serum AREG level is a potential prognostic biomarker in colorectal cancer. We plan to evaluate a larger cohort to confirm the significance of these correlations.
http://dx.doi.org/10.1016/j.ejca.2014.03.271
P0228 KNOWLEDGE, ATTITUDE, AND PRACTICE OF IRANIAN WOMEN TOWARDS BREAST CANCER SCREENING METHODS B. Morshed Behbahani a,*, T. Dadkhah Tehrani b, F. Gharibi c . Department of Midwifery, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran, b Qom University of Medical Sciences, Department of Midwifery, Qom, Iran, c Department of Statistics, Kordestan University of Medical Sciences, Kordestan, Iran a
Background: Female breast cancer is the second leading cause of death due to cancer. Increased use of screening methods has improved the ability to detect non-palpable lesions, and early detection is achievable. Unfortunately, in Iran, breast cancer occurs in younger women and is detected at more advanced stages. We investigated knowledge, attitudes, and practices of Iranian women regarding breast cancer screening, so that more appropriate training programmes can be offered if necessary. Methods: A cross-sectional descriptive study was done of women who were referred to public health centres in the city of Sanandaj. Findings: From 314 questionnaires, 296 women (94.3%) believed that breast cancer is the most common cancer in women. Participants had poor knowledge of breast cancer and screening methods (47.2% had poor knowledge of common symptoms, risk factors, and methods of early detection and diagnosis, 37.8% had average knowledge, and 15% had good knowledge). 55% had a poor attitude toward screening methods, 31.9% had an average attitude, and 13% had a good attitude. More than half (52.6%) of participants had never examined their breasts, and 95.5% did not have or intend to have mammography. According to Spearman’s correlation test, poor positive correlations were detected between the number of pregnancies and knowledge about cancer symptoms (r = 0.14, p < 0.05), knowledge of risk factors for breast cancer (r = 0.23, p < 0.05), and general breast cancer knowledge (r = 0.17, p < 0.05). Interpretation: The results of this study suggest that Iranian women need more education on breast cancer, breast self-examination, and other methods of early detection. Since women’s beliefs and behaviours may have an impact on young women, planning training courses for this group is essential.
http://dx.doi.org/10.1016/j.ejca.2014.03.272
P0229 POSSIBLE INTERACTION BETWEEN HIF-1A AND VGSCS IN AGGRESSIVE BREAST CANCER CELLS H.D. Dewadas *, N.F. Mokhtar. Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Kelantan, Malaysia
Abstracts / 50 (2014) e1–e74
CYP3A5*3 (rs776746) polymorphisms by polymerase chain reaction– restriction fragment-length polymorphisms (PCR–RFLP). Logistic regression analysis was done to calculate risk association using EpiInfo 7.0 software. Findings: The distribution of CYP3A5*3 genotype was 41.5% (GG), 37.7% (GA), and 20.8% (AA) among the IM-resistant group, compared with 45.8% (GG), 33.3% (GA), and 20.9% (AA) among the IM-good-response group. There was no significant difference in genotype frequencies between the two groups (p = 0.91). On evaluating the risk of IM resistance, the frequencies of homozygous TT genotype and heterozygous TC variant of CYP3A4*18 were insignificantly associated with IM response (p = 0.25). Odds ratio was 0.34 (95% confidence interval [CI] 0.062–1.827, p = 0.19) for the CYP3A4*18 heterozygous variant, 1.25 (95% CI 0.516–3.026, p = 0.69) for the CYP3A5*3 heterozygous variant, and 1.10 (95% CI 0.389–3.114, p = 0.86) for the CYP3A5*3 homozygous variant. Interpretation: Our preliminary results suggest a lack of association between CYP3A4*18 and CYP3A5*3 gene polymorphisms and IM resistance. This study is being continued with a larger number of patients.
http://dx.doi.org/10.1016/j.ejca.2014.03.267
P0224 A NOVEL, SMALL MOLECULE INHIBITOR, MSU-1001, IN ANDROGEN-SENSITIVE PROSTATE CANCER CELL LINES P.K. Bhavar a,*, M.R. Yadav a, S.S. Dinavahi b, S. Nyayapathy b. Department of Pharmacy, M.S. University of Baroda, Gujarat, India, b Biological Research Lab, Incozen Therapeutics, Andrapradesh, India a
Introduction: Prostate cancer is one of the leading causes of cancerrelated death in men worldwide. Current treatment options are limited to traditional chemotherapy, surgery, radiation, or hormone therapy, which often have unwanted side effects. There is a need to develop safer molecules that attenuate tumour progression without adversely affecting the overall quality of life. We report the in vitro activity of a novel, synthetic, small molecule, with potential to be a lead candidate for the treatment of prostate cancer. Methods: A library of novel small molecule inhibitors was developed through rational drug design. A pyrrolo-pyrimidine derivative (MSU-1001) was identified as a potential lead molecule. Prostate and colon cancer cell lines (LNCap, HT-29, and HCT-8) were obtained from the American Type Culture Collection (ATCC). Cells were incubated with various concentrations of MSU-1001 for 72 h. Growth inhibition was determined colorimetrically on a plate-reader using a 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Findings: Colon cancer cell lines HCT-8 and HT-29 were used in conjunction with the androgen-sensitive human prostate adenocarcinoma cell line, LNCaP, to investigate the specificity of MSU-1001 on tumour type. Among the library of compounds tested, MSU-1001 was pursued based on its anti-proliferative activity in LNCaP cells. Addition of MSU-1001 to LNCaP cells resulted in a dose-dependent inhibition of proliferation (GI50 = 161 nM) with a near-complete inhibition of cell growth noted at 10 lM. By contrast, GI50 of gemcitabine was more than 6-fold higher (GI50 = 1.21 lM) in LNCaP cells. Additionally, GI50 of MSU-1001 in HCT-8 and HT-29 was 1.8 and 8.7 lM, respectively, indicating relative specificity of MSU-1001 against prostate cancer. Interpretation: These data show the therapeutic potential of MSU-1001 in prostate cancer. Combination studies of MSU-1001 with
testosterone, 17b-estradiol, and dehydroepiandro-stenone in androgen-sensitive and insensitive prostate cancer cell lines are currently ongoing.
http://dx.doi.org/10.1016/j.ejca.2014.03.268
P0225 TELEMEDICINE: A NOVEL APPROACH OF BRINGING ONCOLOGY CARE CLOSER TO THE PATIENT D.M. Poprawski *, J. Adams, A. Bassal. Country Health South Australia Local Health Network (CHSALHN), Elizabeth Vale, SA, Australia Background: In Australia, long distances have motivated oncologists to try innovations in the provision of oncology care to improve cost efficiency, access, and compliance. This study aimed to demonstrate the use of telemedicine, a novel approach of bringing oncology care to regional centres, and its applicability across Asia and Oceania. Methods: A retrospective review of telemedicine clinic use was conducted for two South Australian regional sites (Whyalla and Mount Gambier) over a 12-month period. Findings: Between February 2013 and January 2014, 380 patients were reviewed in oncology telemedicine clinics (n = 152 in Whyalla, n = 228 in Mount Gambier). The average number of patients reviewed per month was 31 (n = 12, n = 19). As oncologists grew comfortable with the consultation technique, the types of consultations conducted by telemedicine were expanded. Numbers by consultation type were: pre-chemotherapy review, n = 285 (n = 135, n = 150); restaging, n = 39 (n = 15, n = 24); and first consultation, n = 6 (n = 2, n = 4). Both men and women were reviewed, age range was 24–87 years, and ethnicities included Indigenous, Australian, European, and Asian. A teleconferencing unit was used in the regional clinic and a computermounted camera at the oncologist’s clinic. The costs to run a telemedicine clinic will be compared to travel costs in a metropolitan-based approach. Interpretation: Telemedicine allows specialists to review patients on a regular basis during chemotherapy, without the need for travel to a major metropolitan centre. Uniformity and simplicity of approach makes telemedicine user-friendly and cost effective for patients and health services. Telemedicine provides a novel technique for safe and efficient oncology care closer to the patient’s home. The technique has clear savings by minimising travel and burden on metropolitan clinic budgets. This approach can be easily adapted to most countries in Asia and Oceania.
http://dx.doi.org/10.1016/j.ejca.2014.03.269
P0226 PATTERNS OF RECURRENCE IN LOCALLY ADVANCED SQUAMOUS CELL CARCINOMAS OF THE HEAD AND NECK AFTER THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY: AN INSTITUTIONAL EXPERIENCE A. Singh *, D.J. Fernandes, M.S. Vidyasagar, S.A. Reddy. Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital, Kasturba Medical College, Manipal, India
Abstracts / 50 (2014) e1–e74
Background: Loco-regional recurrences continue to plague head and neck cancers, even with combined modality treatment. We report patterns of loco-regional recurrence after three-dimensional (3D) conformal radiotherapy among patients with locally advanced (non-nasopharyngeal) head and neck squamous cell cancers. Methods: From 2009 to 2012, 263 patients with stage III–IV head and neck squamous cell carcinoma received treatment at our institute with radical external beam radiotherapy with or without chemotherapy. Patients who had surgical resection of primary tumour or nodal site were excluded. Sites of loco-regional relapses were compared and correlated with radiotherapy treatment plans by the radiation oncologist and medical physics team. Findings: Median follow-up was 38 months (range 3–62). Median patient age was 52 years. After a mean follow-up of 21 months (range 0–44), there were 42 patients with loco-regional failure. The median time to failure among these patients was 12.5 months (range 3–17). Of the 42 cases, 20 failed locally, 17 had regional failure, and five had simultaneous loco-regional failure. 38 patients had in-field recurrence, three had simultaneous in-field and out-of-field recurrence, and one patient had marginal recurrence. Interpretation: In this study, the predominant pattern of recurrence after 3D conformal radiotherapy was in-field. Sites of primary gross disease and nodal levels initially involved were the most common sites of recurrence. Further studies on radio-resistant tumour populations are needed, to enhance early identification and appropriate treatment intensification.
http://dx.doi.org/10.1016/j.ejca.2014.03.270
P0227 UTILITY OF PRE-TREATMENT SERUM AMPHIREGULIN IN COLORECTAL CARCINOMA C. Chayangsu a,*, P. Kanjanasilp b, S. Malakorn b, C. Sahakitrungruang b, S. Tanasanvimon a, P. Sitthideatphaiboon a, V. Sriuranpong a. a Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, b Division of Colorectal Surgery, Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Amphiregulin (AREG) is an EGFR ligand that plays an important role in tumour progression and metastasis. Upregulation of AREG in colon cancer tissue has been correlated with liver metastasis. We investigated the correlation of serum AREG in colorectal cancer with clinico-pathological parameters. Methods: Colorectal cancer patients who received treatment at our institute from September to December 2013 were enrolled. We collected and stored baseline serum before the start of any therapy. Serum AREG was measured by ELISA using Human Amphiregulin DuoSet (R & D Systems, Minneapolis, MN). The correlation between independent clinico-pathological characteristics and serum AREG was analysed. Findings: 40 patients were enrolled and included in the analysis: 25 patients with stage I–III disease and 15 patients with advanced stage disease. In the advanced disease group, the mean level of serum AREG was 65.12 pg/mL (±89.49), which was higher than in the localised disease group (23.68 pg/mL [±37.89], p = 0.11). Serum AREG higher than 40 pg/mL significantly correlated with depth of tumour invasion (pT4) and distant metastases (M), and there was a trend toward association with lymphovascular invasion and perineural invasion.
e73
Interpretation: Serum AREG level is a potential prognostic biomarker in colorectal cancer. We plan to evaluate a larger cohort to confirm the significance of these correlations.
http://dx.doi.org/10.1016/j.ejca.2014.03.271
P0228 KNOWLEDGE, ATTITUDE, AND PRACTICE OF IRANIAN WOMEN TOWARDS BREAST CANCER SCREENING METHODS B. Morshed Behbahani a,*, T. Dadkhah Tehrani b, F. Gharibi c . Department of Midwifery, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran, b Qom University of Medical Sciences, Department of Midwifery, Qom, Iran, c Department of Statistics, Kordestan University of Medical Sciences, Kordestan, Iran a
Background: Female breast cancer is the second leading cause of death due to cancer. Increased use of screening methods has improved the ability to detect non-palpable lesions, and early detection is achievable. Unfortunately, in Iran, breast cancer occurs in younger women and is detected at more advanced stages. We investigated knowledge, attitudes, and practices of Iranian women regarding breast cancer screening, so that more appropriate training programmes can be offered if necessary. Methods: A cross-sectional descriptive study was done of women who were referred to public health centres in the city of Sanandaj. Findings: From 314 questionnaires, 296 women (94.3%) believed that breast cancer is the most common cancer in women. Participants had poor knowledge of breast cancer and screening methods (47.2% had poor knowledge of common symptoms, risk factors, and methods of early detection and diagnosis, 37.8% had average knowledge, and 15% had good knowledge). 55% had a poor attitude toward screening methods, 31.9% had an average attitude, and 13% had a good attitude. More than half (52.6%) of participants had never examined their breasts, and 95.5% did not have or intend to have mammography. According to Spearman’s correlation test, poor positive correlations were detected between the number of pregnancies and knowledge about cancer symptoms (r = 0.14, p < 0.05), knowledge of risk factors for breast cancer (r = 0.23, p < 0.05), and general breast cancer knowledge (r = 0.17, p < 0.05). Interpretation: The results of this study suggest that Iranian women need more education on breast cancer, breast self-examination, and other methods of early detection. Since women’s beliefs and behaviours may have an impact on young women, planning training courses for this group is essential.
http://dx.doi.org/10.1016/j.ejca.2014.03.272
P0229 POSSIBLE INTERACTION BETWEEN HIF-1A AND VGSCS IN AGGRESSIVE BREAST CANCER CELLS H.D. Dewadas *, N.F. Mokhtar. Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Kelantan, Malaysia