ESTRO 2020 Abstract book

S1060 ESTRO 2020

Fig.1 shows the relationship between the mean BWT measured either on dorsal and ventral sides against bladder volume. For bladder volume >1.5 ml, BWT are almost constant and equal to 0.34 mm with maximum variations of about 20%.

PO‐1807 A multicenter assessment of HSPB1 and TGB1 SNPs for hematological toxicity in lung cancer patients O. Muñoz Muñoz 1 , J. Cacicedo 2 , B.D. Delgado Leon 1 , S. Perez Luque 1 , M. Borrego Reina 1 , J.L. Lopez Guerra 1 1 University Hospital Virgen del Rocío, Radiation Oncology, Sevilla, Spain ; 2 University Hospital of Cruces, Radiation Oncology, Barakaldo, Spain Purpose or Objective Radiation therapy (RT) has not been thought to be as appreciably associated with hematologic toxicities (HT) in lung cancer (LC), although irradiation doses to vertebral bone marrow have been understudied to date. HT can compromise the receipt of further chemotherapy and/or RT and hence may impact outcomes. HSPB1 and TGFB1 single nucleotide polymorphisms (SNPs) have been shown to have association with other toxicities in LC patients related to a very different response to RT. The aim of the current study is the assessment of the impact of such SNPs in HT in a multicenter (2 institutions) setting. Material and Methods DNA samples from 330 primary LC patients have been collected prospectively after consultation at the Radiation Oncology Department from February 2013 to December 2018 in order to perform a genotyping analysis seeking associations between HT and HSPB1 (Rs2868370, Rs2868371, Rs7459185, Rs2009836) and TGFB1 (Rs11466338, Rs11466353, Rs1800468, Rs1800469, Rs4803455, Rs8179181, Rs11466343, Rs11466344, Rs8110090) SNPs . From these patients, 292 (89%) received chemotherapy (platinum based) and 131 (40%) was concurrent with RT (median dose 60Gy, range 20-66 Gy). In addition, 46 patients (14%) underwent surgery. All the patients were caucasians, 276 males (84%) and 54 females (16%), the median age was 63 years old (range, 33-83). Median follow-up time for all patients was 21 months (range, 6-76 months). According to the clinical stage, 26 patients (8%) were stage I-II, 125 (38%) were stage IIIA, 157 (48%) were stage IIIB, and 22 (6%) were stage IV. The histologies were 29% (N=94) adenocarcinoma, 41% (N=135) squamous cell carcinoma, 2% (N=6) large cell carcinoma, 3% (N=11) not specified, and 25% small cell LC. Genotype analysis was performed from DNA isolated from blood samples, by real-time polymerase chain reaction (PCR) using TaqMan® SNP Genotyping Assays. The end points (acute HT) of analysis were estimated and scored using Common Terminology Criteria for Adverse Events version 4.0. Cox proportional hazards analysis were performed in order to evaluate the effect of different genotypes on HT. Results Multivariate analysis showed that HSPB1 Rs7459185 CC (vs GG/GC) genotype was associated with lower grade ≥2 thrombocytopenia (5% vs 20%; OR=0.18, P=0.026). HSPB1 Rs2868370 GG genotype (vs GA/AA) was associated with higher grade ≥2 granulocytopenia (25% vs 5%; OR=10.59, P=0.036). TGFB1 Rs8179181 CC genotype (vs CT/TT) was associated with higher grade 3 granulocytopenia (23% vs 11%; OR=2.55, P=0.044) and grade ≥2 anemia (27% vs 11%; OR=2.51, P=0.046). TGFB1 Rs11466338 AA genotype (vs AG/GG) was associated with lower grade ≥2 thrombocytopenia (5% vs 40%; OR=0.06, P=0.012). Conclusion Our findings show a relationship between the functional HSPB1 promoter variant Rs2868370 and Rs7459185 as well as TGFB1 Rs8179181 and Rs11466338 with HT in LC patients. These response markers may be used as biomarkers for future individual therapeutic schemes.

An example of US images of the bladders before and after irradiation is shown in Fig.2. Fully-filled bladders of rats irradiated with 25, 30 and 35 Gy always showed volumes above 1.5 ml, confirming the reliability of the BWT measurements. The average ratios between BWT-post and BWT- pre irradiation were equal to 1.13 ± 0.11, 1.68± 0.16 and 1.35 ± 0.36 for 25, 30 and 35 Gy respectively; of note, 4/6 rats treated with 30-35 Gy showed BWT ratios >1.5, in contrast to rats irradiated with 25 Gy.

Conclusion We demonstrated the feasibility of using US on small animals to detect BWT changes after bladder irradiation. Although preliminary, these results are promising, addressing the potential of this non-invasive approach in quantifying the radiation-induced effects on bladder. Future investigations will focus on the kinetic of the phenomenon over time (likely relying on acute inflammation first and then on a fibrotic process activation) and its relation with urinary functionality and with histological alterations.