No abstract

3559 Background: Recently, conflicting evidence has emerged showing the association of ctDNA level and cancer progression. The aim of our study was the development of a method for detecting ctDNA in plasma and the investigation of the prognostic value of ctDNA retention after surgery in the prospective way. Methods: This prospective, single-center, sample collection study; pts with early-stage malignancies of the different origin were included. Tumor somatic mutations were determined by target sequencing of DNA from FFPE tumor blocks. Sequencing was performed using the custom NGS panel covering regions of frequent somatic mutations in 50 genes. Tumor-specific mutations were monitored in plasma samples taken before and after surgery. The median time between surgery and plasma collection was 7 days (5-15). Mutations of plasma ctDNA were determined by ddPCR. The plasma sample was considered "positive" if the content of ctDNA was more than 0.5 copies of mutant DNA in ml plasma. We needed 265 pts for improving 1-year disease free survival (DFS) from 60% to 80% with α=0.01, β=0.1, 10% loss of f.-up and duration of the study for 2 years. Results: The study comprised 271 pts with various cancers including colorectal – 91 (33,6%), pancreatic – 37 (13,7%), breast – 66 (24,4%), lung – 35 (12,9%) and gastric cancer – 42 (15,5%). Pts with stage I was 50 (18,5%), stage II – 118 (43,5%) and stage III – 103 (38%). The median time of the f.-up was 9 mos. (1-37). No significant association was found between the level of ctDNA before surgery and DFS either in the general group or in groups stratified by tumor sites (HR 2.4, 95%CI 0.8-7.1, р=0.12 and HR 1.5, 95%CI 0.4-6.3, р=0.5, correspondingly). ctDNA was detected in the plasma after surgery in 57 (10%) pts: 9 (9.9%) cases of colorectal, 10 (27%) - pancreatic, 9 (13.6%) - breast, 19 (54.3%) - lung, and 10 (23.8%) - gastric cancer. Progression of the disease was detected in 28/57 (49%) pts with ctDNA(+) and 17/214 (8%) - in ctDNA(-) pts (p<0.001). One-year DFS in ctDNA(+) and ctDNA(-) pts were 57% and 87%, respectively (HR 6.1, 95%CI 3.3-11.2, p<0,001). ctDNA positivity after surgery was an independent negative prognostic factor according to Cox regression model fitted to T, N, and adjuvant chemotherapy (HR 5.7, 95%CI 3.1-10.8, p <0.001). Conclusions: These results demonstrate the prognostic significance of ctDNA persisting after surgery in pts with the early stage of the different malignancies. Further clinical validation of this approach is required in trails with modifications of the adjuvant treatment, according to the content of ctDNA.

Results: 268 patients were included, with male prevalence (165, 61.6%), mean age at diagnosis of 64 y/o (SD¼11.96), and 127 patients were aged 65 or above. The category was ECOG-PS 0 for 215 (80.2%), ECOG-PS1 for 48 (17.9%), and ECOG-PS2 for 5 (1.9%) patients. Anaemia at diagnosis was found in 111 (41.4%) patients. Diabetes was described for 51 (19%), heart disease 39 (14.6%), vascular disease 115 (42.9%), alcohol consumption 66 (24.6%), and smokers 88 (32.8%). Age-adjusted comorbidity index was 6 or higher for 92 (34.3%) patients. The tumour was located at the low rectum in 113 (42.1%), medium 71 (26.5%), and proximal 84 (31.3%) patients. The mean follow-up time was 34 months (SD¼19.27). Regarding treatment approach, the most frequent was long-course neoadjuvant CRT (210, 78.4%), and the remaining were short course neadjuvant RT (27, 10.1%), adjuvant RT plus CHT (28, 10.4%), and adjuvant RT (3, 1.1%). Only 2 patients did not receive CHT. AUROC analysis showed the discriminative values of NLR>3.36 and NLR>3.36, for 5y-OS and 5y-DSS, respectively. Cox analysis revealed that patients with NLR above 3.36, were at higher risk for death related to rectal cancer [HR¼2.07; 95%CI 1.04-4.14, p¼0.039] and for all cause-death [HR¼1.93; 95%CI 1.05-3.54, p¼0.033]. The NLR cut-off estimated for our cohort (>3.36) was compared with other ones described in the literature (NLR>3.0). Eighty-two (30.6%) patients had NLR>3.36 and for 102 (38.1%) NLR was higher than 3. For those patients with NLR 3.36 and >3.36, the 5y-DSS was 79,2% and 46.3% [p(log-rank) 3.0, respectively. For the patients with NLR 3.36 and >3.36, the 5y-OS was 73.3% and 56.0% [p(log-rank) 3.0, respectively. Conclusion:Our data are in accordance with recent studies, affirming the predictive role of NLR for rectal cancer patients treated with curative intent. The AUROC discriminative value of NLR we found overwrites the existing reports in the literature. Regarding survival patterns, there were no significant differences between NLR>3.0 and NLR>3.6.Legal entity responsible for the study: The author.

2Акромегалия -редкое заболевание, характери-зующееся повышенной секрецией соматотроп-ного гормона, что наиболее часто обусловле-но наличием аденомы гипофиза. Отсутствие своевременного лечения акромегалии ведет к преждевременной смерти больных, связан-ной с повышением частоты развития острых сердечно-сосудистых осложнений, апноэ сна, метаболических нарушений и злокачественных новообразований. Частота злокачественных новообразований при акромегалии состав-ляет от 4,5 до 25% (при этом механизмы их развития имеют ряд отличительных особенно-стей), в 9-50% случаев они становятся причи-ной гибели пациентов. При акромегалии общая смертность и смертность от онкологических за-болеваний коррелирует с активностью заболе-вания. Установлена прямая зависимость между высоким уровнем инсулиноподобного росто-вого фактора 1 крови и риском развития злока-чественных опухолей. У больных акромегалией наиболее часто встречаются злокачественные новообразования толстого кишечника (1-20%) и щитовидной железы (7,8-11%). В обзоре ли-тературы отражены результаты эпидемиоло-гических исследований злокачественных но-вообразований, а также некоторые аспекты их патогенеза у больных акромегалией.Ключевые слова: акромегалия, злокачествен-ные новообразования, инсулиноподобный ро-стовой фактор 1, соматотропный гормон, коло-ректальный рак, рак щитовидной железы, рак молочной железы

ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEM