6 research outputs found

    Early echocardiographic alterations in cancer patients during chemotherapy

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    Aim. To evaluate the early manifestation of cardiotoxicity after the first course of multiagent chemotherapy (MAC) using echocardiography with an assessment of the left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS).Material and methods. The study included 49 cancer patients with elective MAC.Results. After the first administration of a therapeutic dose of chemotherapy, a decrease in LVEF ≥10 and GLS >15 was demonstrated in more than 6,1% of patients, as well as a subclinical decrease in LVEF ≥5% in 22,4% and a decrease in GLS ≥12% in 24,5%.Conclusion. In cancer patients, after the first course of chemotherapy, GLS dynamics should be assessed during echocardiography as a marker of myocardial dysfunction

    Resolution on the results of Advisory Board “Searching the effective methods of testing and treating patients with NSCLC caused by <i>NTRK</i> gene fusions“

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    The Advisory Board was held on December 24, 2021. The molecular genetic research lead specialists and national lead oncologists discussed issues of diagnosis of NTRK gene translocations in patients with non-small cell lung cancer (NSCLC), as well as current opportunities for the treatment of patients with NSCLC caused by NTRK gene fusions. The experts reaffirmed the necessity to identify timely patients with NSCLC caused by NTRK gene fusions, as the correct diagnosis of the disease, including the use of modern diagnostic methods of NTRK gene fusion (NGS is the most sensitive and specific method) determines the success of patient treatment. In this regard, it is critical that physicians know the advantages and disadvantages of each molecular diagnostic method used to have the opportunity to choose the best approach in each clinical case. In order to have a clear, well-functioning strategy for managing patients with suspected NSCLC caused by NTRK gene fusion, it is necessary to use molecular genetic tests, as well as include TRK inhibitors (in particular, the drug larotrectinib; at the time publication of the Resolution, the drug larotrectinib is not registered in the territory of the Russian Federation) in the clinical guidelines for the treatment of lung cancer. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor. The clinical studies on larotrectinib have demonstrated high response rates and durable responses in adults and children with tumours associated with NTRK gene fusions, including primary CNS tumours and brain metastases. The objective response rate observed with larotrectinib was 79%, with 16% achieving a complete response and 64% achieving a partial response. At the same time, the median progression-free survival on larotrectinib was 28.3 months, and the median overall survival was 44.4 months

    РЕЗУЛЬТАТЫ ДОБАВЛЕНИЯ ПАНИТУМУМАБА К КОНВЕРСИОННОЙ ТЕРАПИИ КОЛОРЕКТАЛЬНОГО РАКА С МЕТАСТАЗАМИ В ПЕЧЕНЬ

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    Panitumumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer.Our purpose was to evaluate whether panitumumab is effective and safe in patients with potentially resectable colorectal liver metastases (CRLM).Methods. Consecutive analysis of data from 11 patients (KRAS wild) receiving oxaliplatin-based chemotherapy and panitumumab as converse preoperative treatment for potentially resectable CRLM. At the moment of presentation R0-liver resection was not possible due to technical reasons (small remnant volume, large liver vessels involvement etc.). We studied objective response rate, surgical characteristics, skin toxicity profile, and perioperative course. Also expression of EGFR-ligands (transforming growth factor-α and amphiregulin) and   expression of E-cadherin were studied.Results. After median 6 courses of treatment, metastatic liver tumors were reduced considerably (PR) in 8 pts (73 %). Radical liver resection (R0) with 3 median number of removed segments was done in 6 (55 %) patients. Two pts underwent successfully the two-stage surgery (1 – portal vein embolization and 1 – portal vein ligation with partial left resection). Two patients progressed on chemotherapy (18 %). There was no correlation between skin toxicity and response. Mean blood loss was 250 ml. Preoperative administration of panitumumab was associated with higher risk of postoperative infection complication (57.1 %).Conclusions. To the best of our knowledge this is the first report about using panitumumab as conversion therapy before liver resection. The panitumumab and oxaliplatine-based regimen may increase the resection rate of liver metastases and influence on adhesive and proliferative activity of cancer cells. It is necessary to focus on postoperative infection complications.Доказано, что панитумумаб увеличивает выживаемость без прогрессирования и общую выживаемость у пациентов с метастазами колоректального рака (КРР) в печень.Целью нашего исследования стала оценка безопасности и эффективности добавления панитумумаба к лечению пациентов с потенциально резектабельными метастазами.Методы. В когортное проспективное исследование были включены 11 пациентов (дикий тип KRAS) с метастазами КРР в печень, расцененные исходно как «потенциально резектабельные» и получившие в качестве конверсионной предоперационной терапии панитумумаб в сочетании с химиотерапией на основе оксалиплатина в отделении хирургии печени, поджелудочной железы и желчных путей ФГБУ «РНЦХ им. акад. Б.В. Петровского» РАМН. К исследуемым параметрам относились частота и процент объективного ответа по критериям RECIST 1.1, оценка частоты выполнения резекции в объеме R0, интраоперационные и послеоперационные показатели, такие как кровопотеря во время операции, продолжительность операции, длительность пребывания в стационаре, осложнения, 30-дневная и 90-дневная летальность. Также изучалась экспрессия лигандов рецептора эпидермального фактора роста (EGFR) – трансформирующего фактора роста и амфирегулина, а также E-кадгерина.Результаты. После в среднем 6 курсов лечения частичный объективный ответ был зарегистрирован в 73 % случаев. Радикальную резекцию печени с удалением в среднем 3 сегментов удалось выполнить в один этап у 6 (55 %) пациентов. Два пациента успешно завершили двухэтапное лечение (1 – эмболизация воротной вены и 1 – перевязка правой воротной вены с сегментарной левосторонней резекцией). У 2 пациентов была зафиксирована прогрессия на фоне лечения. Корреляция между степенью выраженности кожной токсичности и объективным ответом отсутствовала. Медиана кровопотери составила 250 мл. Предоперационная терапия панитумумабом сопровождалась повышенным риском послеоперационных инфекционных осложнений (57,1 %).Выводы. По нашим данным, это первое исследование, в котором изучалось добавление панитумумаба к конверсионной терапии метастатического КРР до резекции печени. Режим лечения с использованием панитумумаба и оксалиплатина может увеличить частоту успешных резекций печени и влиять на адгезивные и пролиферативные свойства опухолевых клеток. Необходимо уделять внимание возможности развития послеоперационных инфекционных осложнений.

    RESULTS OF PANITUMUMAB ADDITION TO CONVERSION THERAPY FOR COLORECTAL CANCER LIVER METASTASES

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    Panitumumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer.Our purpose was to evaluate whether panitumumab is effective and safe in patients with potentially resectable colorectal liver metastases (CRLM).Methods. Consecutive analysis of data from 11 patients (KRAS wild) receiving oxaliplatin-based chemotherapy and panitumumab as converse preoperative treatment for potentially resectable CRLM. At the moment of presentation R0-liver resection was not possible due to technical reasons (small remnant volume, large liver vessels involvement etc.). We studied objective response rate, surgical characteristics, skin toxicity profile, and perioperative course. Also expression of EGFR-ligands (transforming growth factor-α and amphiregulin) and   expression of E-cadherin were studied.Results. After median 6 courses of treatment, metastatic liver tumors were reduced considerably (PR) in 8 pts (73 %). Radical liver resection (R0) with 3 median number of removed segments was done in 6 (55 %) patients. Two pts underwent successfully the two-stage surgery (1 – portal vein embolization and 1 – portal vein ligation with partial left resection). Two patients progressed on chemotherapy (18 %). There was no correlation between skin toxicity and response. Mean blood loss was 250 ml. Preoperative administration of panitumumab was associated with higher risk of postoperative infection complication (57.1 %).Conclusions. To the best of our knowledge this is the first report about using panitumumab as conversion therapy before liver resection. The panitumumab and oxaliplatine-based regimen may increase the resection rate of liver metastases and influence on adhesive and proliferative activity of cancer cells. It is necessary to focus on postoperative infection complications

    Disparity between Inter-Patient Molecular Heterogeneity and Repertoires of Target Drugs Used for Different Types of Cancer in Clinical Oncology

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    Inter-patient molecular heterogeneity is the major declared driver of an expanding variety of anticancer drugs and personalizing their prescriptions. Here, we compared interpatient molecular heterogeneities of tumors and repertoires of drugs or their molecular targets currently in use in clinical oncology. We estimated molecular heterogeneity using genomic (whole exome sequencing) and transcriptomic (RNA sequencing) data for 4890 tumors taken from The Cancer Genome Atlas database. For thirteen major cancer types, we compared heterogeneities at the levels of mutations and gene expression with the repertoires of targeted therapeutics and their molecular targets accepted by the current guidelines in oncology. Totally, 85 drugs were investigated, collectively covering 82 individual molecular targets. For the first time, we showed that the repertoires of molecular targets of accepted drugs did not correlate with molecular heterogeneities of different cancer types. On the other hand, we found that the clinical recommendations for the available cancer drugs were strongly congruent with the gene expression but not gene mutation patterns. We detected the best match among the drugs usage recommendations and molecular patterns for the kidney, stomach, bladder, ovarian and endometrial cancers. In contrast, brain tumors, prostate and colorectal cancers showed the lowest match. These findings provide a theoretical basis for reconsidering usage of targeted therapeutics and intensifying drug repurposing efforts
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