Page 375 - 2014 Printable Abstract Book
P. 375
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10-15. Platelet counts of less than 5.67×10 /μl and absolute neutrophil counts of less than 0.026×10 /μl
during this period correlated with mortality. Enrofloxacin was initiated earlier in population-based
therapy, on day 5 vs days 9-16, (mean day 12) with subject-based therapy. Despite a shorter duration of
antibiotics, mortalities were fewer in the subject-based care group. These data suggest that strategic
blood transfusions, administered between days 10-15 post-radiation based on need, may provide
significant survival gains in subjects exposed to high doses of radiation. This project has been funded in
whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority,
Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of
Health and Human Services, under Contract No. HHSO100200800061C and NIAID Study No. AYR13, RFP-
NIH-NIAID-DAIT-05-037.
(PS7-39) Variants in radioresponsive genes influence the radiotherapy induced normal tissue adverse
1
1
reactions in breast cancer. Bola Sadashiva Satish. Rao, MSc, PhD ; Kamalesh Dattaram. Mumbrekar, MSc ;
2
4
Donald Jerard. Fernandes, MD ; Shama Prasada Kabekoddu, MSc, PhD ; Fumiaki Nakayama, MD, PhD ;
3
5
4
3
Vadhiraja Manjunath. Bejadi, MD ; Takashi Imai, PhD ; and Kapaettu Satyamoorthy, MSc, PhD
Division of Radiobiology & Toxicology, School of Life Sciences, Manipal University, Manipal, India ;
1
Department of Radiotherapy & Oncology, Shirdi Saibaba Cancer Hospital and Research Centre, Kasturba
2
Hospital, Manipal, India ; Division of Biotechnology, School of Life Sciences, Manipal University, Manipal,
3
India ; Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy,
5
4
National Institute of Radiological Sciences, Chiba, Japan ; and Manipal Hospital, Bangalore, India
Heterogeneity in normal tissue toxicity is observed in cancer patients after radiotherapy (RT) and
the severe normal tissue toxicity limits the therapeutic outcome. Response to ionizing radiation involves
various genes from vivid pathways involving DNA damage and its repair, inflammatory cytokine, cell cycle
regulation, antioxidant response etc. Therefore, the common sequence variants in these radioresponse
genes may modify the severity of normal tissue toxicity and understanding their association may have
clinical relevance as a predictive biomarker. The present study was aimed to evaluate the potential
modifying role of genetic variants in NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A,
LIG3, SH3GL1, BAXS, XRCC1, MAD2L2 and TGFBR3 genes on the individual susceptibility to RT induced
acute skin reactions. All the 121 breast cancer patients were treated by a 3-dimensional conformal RT
technique. Patients received a total dose of 50 Gy in case of mastectomy and 60 Gy in breast conservation
surgery. The severity of skin damage was scored according to the Radiation Therapy Oncology Group
(RTOG) criteria and the toxicity scores were dichotomized as non-over-responders (NOR) (<2) and over-
responders (OR) (≥2) for analysis. Out of the 121 subjects, the percentages of patients experiencing RTOG
grade 0, 1, 2, 3, and 4 acute skin reactions were 9.9% (n=12), 54.5% (n=66), 28.1% (n=34), 7.4% (n=9), and
0%, respectively. Among the 20 studied, only rs8193 (CD44) polymorphism was significantly (p<0.05)
associated with the radiotherapy induced adverse skin reactions. Acknowledgements: The financial
support from DBT (BT/01/COE/06/02/07), India-Japan Cooperative Science Program (IJCSP) from DST,
Government of India to carry out this research work and Manipal University for providing the research
facilities is gratefully acknowledged.
373 | P a g e
3
10-15. Platelet counts of less than 5.67×10 /μl and absolute neutrophil counts of less than 0.026×10 /μl
during this period correlated with mortality. Enrofloxacin was initiated earlier in population-based
therapy, on day 5 vs days 9-16, (mean day 12) with subject-based therapy. Despite a shorter duration of
antibiotics, mortalities were fewer in the subject-based care group. These data suggest that strategic
blood transfusions, administered between days 10-15 post-radiation based on need, may provide
significant survival gains in subjects exposed to high doses of radiation. This project has been funded in
whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority,
Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of
Health and Human Services, under Contract No. HHSO100200800061C and NIAID Study No. AYR13, RFP-
NIH-NIAID-DAIT-05-037.
(PS7-39) Variants in radioresponsive genes influence the radiotherapy induced normal tissue adverse
1
1
reactions in breast cancer. Bola Sadashiva Satish. Rao, MSc, PhD ; Kamalesh Dattaram. Mumbrekar, MSc ;
2
4
Donald Jerard. Fernandes, MD ; Shama Prasada Kabekoddu, MSc, PhD ; Fumiaki Nakayama, MD, PhD ;
3
5
4
3
Vadhiraja Manjunath. Bejadi, MD ; Takashi Imai, PhD ; and Kapaettu Satyamoorthy, MSc, PhD
Division of Radiobiology & Toxicology, School of Life Sciences, Manipal University, Manipal, India ;
1
Department of Radiotherapy & Oncology, Shirdi Saibaba Cancer Hospital and Research Centre, Kasturba
2
Hospital, Manipal, India ; Division of Biotechnology, School of Life Sciences, Manipal University, Manipal,
3
India ; Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy,
5
4
National Institute of Radiological Sciences, Chiba, Japan ; and Manipal Hospital, Bangalore, India
Heterogeneity in normal tissue toxicity is observed in cancer patients after radiotherapy (RT) and
the severe normal tissue toxicity limits the therapeutic outcome. Response to ionizing radiation involves
various genes from vivid pathways involving DNA damage and its repair, inflammatory cytokine, cell cycle
regulation, antioxidant response etc. Therefore, the common sequence variants in these radioresponse
genes may modify the severity of normal tissue toxicity and understanding their association may have
clinical relevance as a predictive biomarker. The present study was aimed to evaluate the potential
modifying role of genetic variants in NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A,
LIG3, SH3GL1, BAXS, XRCC1, MAD2L2 and TGFBR3 genes on the individual susceptibility to RT induced
acute skin reactions. All the 121 breast cancer patients were treated by a 3-dimensional conformal RT
technique. Patients received a total dose of 50 Gy in case of mastectomy and 60 Gy in breast conservation
surgery. The severity of skin damage was scored according to the Radiation Therapy Oncology Group
(RTOG) criteria and the toxicity scores were dichotomized as non-over-responders (NOR) (<2) and over-
responders (OR) (≥2) for analysis. Out of the 121 subjects, the percentages of patients experiencing RTOG
grade 0, 1, 2, 3, and 4 acute skin reactions were 9.9% (n=12), 54.5% (n=66), 28.1% (n=34), 7.4% (n=9), and
0%, respectively. Among the 20 studied, only rs8193 (CD44) polymorphism was significantly (p<0.05)
associated with the radiotherapy induced adverse skin reactions. Acknowledgements: The financial
support from DBT (BT/01/COE/06/02/07), India-Japan Cooperative Science Program (IJCSP) from DST,
Government of India to carry out this research work and Manipal University for providing the research
facilities is gratefully acknowledged.
373 | P a g e
