Морфологическое обоснование применения интраоперационной лучевой терапии для профилактики локорегионального рецидива у больных с протоковой аденокарциномой поджелудочной железы

Background. It is well recognized that pancreatic ductal adenocarcinoma (PDAC) is associated with very poor prognosis, early locoregional invasion and distant metastases. One reason for this is the proliferation of tumor growth through perineural spaces.Aim. To evaluate the efficacy of intraoperative radiation therapy (IORT) for the extrapancreatic perineural invasion (EPPI) in the development of locoregional recurrence in patients with PDAC. Results. In 14.5% (22/152) the tumor was pT1–2, pN0, extraPn 0, R0. R1 detected in 32.1% (49/152). ExtraPn was detected in 36.8% of cases (56/152). Metastases in regional lymph nodes was found in 62.5% (95/152) of cases. In the study of autopsybasic morphological parameters speakers include locoregional tumor progression and / or a distant progression. Locoregional recurrence was found in 85% of cases (29/34), which is manifested by the presence of perineural invasion. The mean time from surgery until locoregional recurrence without extraPn –14 months, with the presence of extraPn – 9 months.Conclusion. Thus, the absence of regional lymph nodes and/or with positive surgical margin does not preclude the development of locoregional recurrence in patients with PDAC. This is what necessitates a combined approach to the treatment of these patients, including surgery, supplemented by conducting IORT that effectively influences on tissues and reduces the number of local recurrence.Введение. Протоковая аденокарцинома поджелудочной железы ассоциируется с очень плохим прогнозом, ранней локорегиональной инвазией и быстрым развитием отдаленных метастазов. Одной из причин этого является высокая частота периневральной инвазии. Цель. В данном исследовании показана необходимость комбинированного подхода к лечению больных с протоковой аденокарциномой поджелудочной железы в видеприменения радикального хирургического вмешательства, дополненного ИОЛТ.Результаты. В 14,5% (22/152) можно утверждать об ограничении опухоли в пределах ПЖ, что соответствует рТ 1–2, pN0, extraPn 0, R0. Показатель R1 обнаружен в 32,1% случаев (49/152). Экстрапанкреатическая периневральная инвазия выявлена в 36,8% случаев (56/152). Метастазы в региональных лимфатических узлах  бнаружили в 62,5% (95/152) случаев ПАК ПЖ. При исследовании аутопсийного материалаосновные морфологические параметры динамики опухоли включают локорегионарную прогрессию и/или дистантную прогрессию. Локорегионарный рецидив обнаружен в 85% случаев (29/34), проявляющийся наличием экстарпанкреатической периневральной инвазии в ложе удаленной опухоли. Среднее время от оперативного лечения до локорегионарного рецидива без extraPn – 14 месяцев, с наличием extraPn – 9 месяцев.Выводы. Локорегионарный рецидив у больных непосредственно cвязан с наличием именно экстрапериневральной инвазии. Выявленная субпопуляция больных без дистантной прогрессии, а только с наличием локорегионарного распространения, диктует необходимость применения комбинированного подхода с обязательным использованием ИОЛТ для достижения максимального эффекта от проведенного хирургического лечения и увеличения продолжительности жизни больных с протоковым раком поджелудочной железы

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health