Оценка эффективности хирургического метода у больных с EGFR-мутированной аденокарциномой легкого III–IV стадии после терапии ингибиторами тирозинкиназы

Objective. To assess the overall and disease-free survival rates in patients with EGFR-mutated lung adenocarcinoma, who underwent surgery after achieving the objective response to tyrosine kinase inhibitor (TKI) therapy.Material and Methods. The overall and disease-free survival rates were analyzed in 18 patients with EGFR-positive lung adenocarcinoma, which was inoperable at presentation due to locally advanced disease or the evidence of distant metastasis. In accordance with the clinical standards, patients were recommended for TKI therapy. Surgical resection was performed after achieving the objective tumor response to TKI therapy. The control group included 23 patients with EGFR mutation-positive lung adenocarcinoma, who did not undergo surgery after receiving TKI therapy.Results. The study revealed a statistically significant effect of surgical resection on the overall survival (OS) in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma after response to TKI therapy (p=0.004). However, there was no statistically significant effect on the disease-free survival (DFS) (p=0.40). There was a tendency to increase in the median OS in patients of the study group (46 months) compared to that in patients of the control group (26 months). Surgery in the study group was characterized with some technical difficulties associated with severe fibrosis. However, this did not affect the duration of surgery and the volume of blood loss.Conclusion. Tumor resection in patients with EGFR mutation-positive stage III–IV lung adenocarcinoma is feasible and safe, but requires highly qualified team surgeons in well-equipped medical centers. Our study revealed that the combination of EGFR-TKI and tumor resection provided better PFS and OS than EGFR-TKI alone. However, further studies are required.Цель исследования ‒ оценить показатели общей и безрецидивной выживаемости у пациентов с EGFR-мутированной аденокарциномой легкого, у которых выполнено хирургическое вмешательство после развития объективного ответа на прием ингибиторов тирозинкиназы (ИТК).Материал и методы. Проанализированы показатели общей и безрецидивной выживаемости 18 больных аденокарциномой легкого с наличием активирующей EGFR-мутации, изначально неоперабельных из-за местнораспространенного опухолевого процесса или наличия отдаленного метастазирования. В соответствии со стандартами оказания специализированной медицинской помощи пациентам был рекомендован прием ИТК. Выполнение хирургических вмешательств оказалось возможным после получения объективного ответа опухоли («stage down») на таргетную терапию. В группу сравнения включено 23 больных аденокарциномой легкого с EGFR-позитивным мутационным статусом, получавших ИТК, но без оперативного вмешательства.Результаты. Выявлено значимое влияние хирургического вмешательства на показатели общей выживаемости (ОВ) у больных EGFR-мутированной аденокарциномой легкого III–IV стадии после приема ИТК (р=0,004). Однако значимого влияния на безрецидивную выживаемость (БРВ) не отмечено (р=0,40). Выявлена тенденция к увеличению медианы ОВ у пациентов исследуемой группы (46 мес) по сравнению с контрольной группой (26 мес). По сравнению со стандартным объемом хирургического вмешательства операции, выполненные у исследуемой группы пациентов, отличались техническими сложностями, связанными с выраженным фиброзом при выделении элементов корня легкого и выполнении лимфодиссекции, но не отличались по длительности и объему кровопотери.Заключение. Хирургические вмешательства у больных с EGFR-мутированной аденокарциномой легкого III–IV стадии технически выполнимы и безопасны, но для их проведения необходимы опытные бригады специалистов и хорошо оснащенные медицинские центры. Статистические данные свидетельствуют о значимом росте показателей выживаемости после операций как компонента комплексного лечения у данной когорты больных, с использованием ИТК, однако данное направление требует дальнейшего изучения

Final report on key comparison CCQM-K55.c (L-(+)-Valine): Characterization of organic substances for chemical purity

Under the auspices of the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a key comparison, CCQM K55.c, was coordinated by the Bureau International des Poids et Mesures (BIPM) in 2012. Twenty National Measurement Institutes or Designated Institutes and the BIPM participated. Participants were required to assign the mass fraction of valine present as the main component in the comparison sample for CCQM-K55.c. The comparison samples were prepared from analytical grade L-valine purchased from a commercial supplier and used as provided without further treatment or purification. Valine was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of organic compounds of low structural complexity [molecular weight range 100–300] and high polarity (pKOW > −2). The KCRV for the valine content of the material was 992.0 mg/g with a combined standard uncertainty of 0.3 mg/g. The key comparison reference value (KCRV) was assigned by combination of KCRVs assigned from participant results for each orthogonal impurity class. The relative expanded uncertainties reported by laboratories having results consistent with the KCRV ranged from 1 mg/g to 6 mg/g when using mass balance based approaches alone, 2 mg/g to 7 mg/g using quantitative 1H NMR (qNMR) based approaches and from 1 mg/g to 2.5 mg/g when a result obtained by a mass balance method was combined with a separate qNMR result. The material provided several analytical challenges. In addition to the need to identify and quantify various related amino acid impurities including leucine, isoleucine, alanine and α-amino butyrate, care was required to select appropriate conditions for performing Karl Fischer titration assay for water content to avoid bias due to in situ formation of water by self-condensation under the assay conditions. It also proved to be a challenging compound for purity assignment by qNMR techniques. There was overall excellent agreement between participants in the identification and the quantification of the total and individual related structure impurities, water content, residual solvent and total non-volatile content of the sample. Appropriate technical justifications were developed to rationalise observed discrepancies in the limited cases where methodology differences led to inconsistent results. The comparison demonstrated that to perform a qNMR purity assignment the selection of appropriate parameters and an understanding of their potential influence on the assigned value is critical for reliable implementation of the method, particularly when one or more of the peaks to be quantified consist of complex multiplet signals.JRC.D.2-Standards for Innovation and sustainable Developmen