Early echocardiographic alterations in cancer patients during chemotherapy

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

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

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.

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“

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

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of &gt;0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants

Systemic Essential Metal and Metalloid Levels in Patients with Benign Breast Disease and Breast Cancer

The objective of the present study is evaluation of serum and hair levels of essential metals and metalloids in women with benign breast disease and breast cancer in order to define similar and distinct patterns that may mediate the link between these pathologies. A total of 310 adult women aged 20–80 years old were enrolled in the present study. Of those, 103 patients had benign (fibrocystic) breast disease, 107 patients had breast cancer (stage II), and 100 women were healthy and with absence of breast pathology. Trace metal and metalloid levels in hair and serum were evaluated by inductively coupled argon plasma mass-spectrometry (ICP-MS). The data demonstrate that breast cancer patients were characterized by significantly higher hair Cr and V levels, as well as reduced Cu and Mn content as compared to both benign breast disease patients and controls. In contrast, serum Cu levels in women with breast cancer exceeded those in the controls and benign breast disease cases. Patients with both benign and malignant breast tumors were characterized by lower serum Mn levels as compared to the control values. Serum Cu/Zn and especially Cu/Mn were found to be significantly increased in cancer patients. Significantly reduced hair and serum Se levels were noted only in women with fibrocystic disease. Based on the analysis of two biosamples, it is proposed that malignant breast tumor development is associated with the reduction of systemic Mn and Zn levels, and a concomitant elevation of Cu concentrations. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

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

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

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

COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer

COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE)

Background: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients and methods: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. Results: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) &amp;lt;25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. Conclusions: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer. © 2022 The Author

COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases.

COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index &lt;25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage. The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality