Imuno-oncologia, un progres major in tratarea cancerului

Gastric cancer unmet needs. Supliment II JTMR

Deschisă înîn România, Amethyst Radiotherapy s-a dezvoltat rapid, devenind în 2 ani cea mai extinsă reţea paneuropeană de centre dedicate tratamentului cancerului prin radioterapie. În prezent, reţeaua Amethyst are 6 clinici deschise în 4 ţări, cumulând 10 acceleratoare liniare şi 4 echipamente de brahiterapie. La nivel european, printre cele mai frecvente tipuri de cancer tratate în cadrul Amethyst Radiotherapy se numără cancerul de sân, urmat de cel de prostată şi plămâni.

Is FLOT the only standard in the perioperative setting for gastric cancer?

În România, la acestea se adaugă tumorile la nivelul colului uterin şi ORL. Deşi tratamentul modern este disponibil în România la preţuri mult mai mici decât în străinătate, lipsa unui comportament preventiv screening periodic este unul din factorii ce conduc la depistarea cancerului în stadii extrem de avansate, ceea ce reduce gastric cancer unmet needs de vindecare completă.

Christian Chiricuţă, directorul medical al Amethyst Radiotherapy România. Christian Chiricuţă. Pacienţii beneficiază de un plan complet de tratament prin radioterapie, care include consulturile medicale pre şi intraterapeutice, analiza dosarului medical, stabilirea strategiei de tratament în comisia oncologică, efectuarea CT-ului de 6 planning, conturarea organelor de risc şi volumul tumoral, stabilirea obiectivelor şi a restricţiilor de doză, efectuarea calculului dozimetric şi verificarea dozimetrică, şedinţele de iradiere, asigurarea şi controlul calităţii.

Amethyst Radiotherapy oferă pacienţilor bolnavi de cancer din Europa tratamente complexe şi complete de radioterapie de tip IMRT — VMAT - una dintre cele mai precise şi rapide gastric cancer unmet needs de radioterapie.

gastric cancer unmet needs

Practica medicală a dovedit astfel că şansele de reuşită în tratarea pacienţilor oncologici sunt mult mai mari decât în cazul unei abordări clasice, unidisciplinare.

În cadrul Amethyst, prof. Christian Chiricuţă este director medical şi şef al Comisiei oncologice alcătuite din experţi radioterapeuţi, fizicieni, gastric cancer unmet needs, radiologi, chirurgi cu o pregătire excepţională în ţară şi gastric cancer unmet needs străinătate, membri atât ai Societăţii Române de Radioterapie şi Oncologie Medicală, cât şi a celei europene şi americane.

Amethyst Radiotherapy este liderul paneuropean gastric cancer unmet needs tratarea cancerului prin radioterapie, operând în prezent 6 clinici în România, Polonia, Germania şi Franţa. Compania îşi propune să continue extinderea reţelei de clinici în Europa.

Carcinomul cu celule Merkel - Tot ce trebuie să ştii | Cancer

Prin tehnologie de ultimă generaţie, experţi de renume european şi prin parteneriatele cu centre de excelenţă precum Centrul de Oncologie Davidoff din Gastric cancer unmet needs Aviv, Universitatea Wurzburg din Germania şi Institutul European de Oncologie de la Milano IEOAmethyst Radiotherapy asigură pacienţilor tratamente gastric cancer unmet needs standarde internaţionale de vârf din domeniu.

Gabriel Doru Ghizdăvescu medic primar Oncologie Medicală, şef Secţie Oncologie, Spitalul Schuller Ploieşti Abstract Rezumat Anticancer therapy is now more effective than ever before, but with the price of important side efects, chief amongst these being cardiovascular side effects. Over the last years, the significance of the cardiac toxicity of anticancer treatment has markedly increased due to improvements in patient survival, aging of the population including cancer patients and the introduction of new anticancer drugs with unique gastric cancer unmet needs.

Following cancer treatment in many patients the risk of cardiovascular death may be higher than the actual risk of tumor recurrence. Cardiotoxicity is defined as the entirety of significant cardiovascular side effects secondary to anticancer treatment, characterised by the decrease in LVEF, responsible for increased morbidity and mortality.

The most frequent and serious side effect is heart failure with ventricular systolic dysfunction.

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Other important toxic effects are hypertension, thromboembolic disease, pericardial disease, arrhythmias and myocardial ischemia. Cardiotoxicity can be classified as non-reversible that leads to progressive systolic heart failure and is most typically caused by anthracyclines and reversible cardiac dysfunction that resolves for most patients over time by interrupting anticancer therapy and administering specific cardiac treatment the best known anticancer agent that causes reversible cardiotoxicity is trastuzumab.

All patients undergoing chemotherapy should have prior careful clinic evaluation and assessment of CV risk factors or comorbidities, as well as routine ECG and baseline Doppler echocardiogram. Keywords: anticancer therapy, cardiotoxicity, cardiovascular side effects Terapia gastric cancer unmet needs este acum mai eficace decât oricând, dar cu preţul unor efecte adverse importante, pe primul loc situându-se efectele secundare cardiovasculare.

gastric cancer unmet needs

Semnificaţia cardiotoxicităţii gastric cancer unmet needs tot mai importantă datorită creşterii supravieţuirii globale inclusiv a gastric cancer unmet needs neoplaziciapariţiei cancerului la vârste înaintate şi datorită introducerii unor noi agenţi terapeutici cu toxicităţi cardiovasculare importante, ajungându-se în situaţia în care la mulţi pacienţi riscul de gastric cancer unmet needs prin boli cardiovasculare să fie mai mare decât riscul de recurenţă a cancerului.

Cardiotoxicitatea se defineşte prin totalitatea efectelor adverse cardiovasculare semnificative secundare tratamentului antineoplazic, ca­rac­terizate de scăderea FEVS, responsabile de mor­bi­di­ta­te și mortalitate. Cel mai important efect advers îl re­pre­zintă insuficienţa cardiacă congestivă. Alte efecte se­cun­dare importante sunt reprezentate de HTA, boala tromboembolică, pericardita, aritmiile, ischemia miocardică.

Din punct de vedere al tipului de cardiotoxicitate, se întâlnesc tipul ireversibil cu progresie spre insuficienţă cardiacă ge­ ne­rată în principal de antracicline şi gastric cancer unmet needs reversibil în care disfuncţia cardiacă se remite prin întreruperea ad­mi­nistrării terapiei antineoplazice şi administrarea de tra­tament specific cardiologic cel mai cunoscut agent an­tineoplazic care produce cardiotoxicitate reversibilă fiind trastuzumab.

În practică, este necesară evaluarea cli­nică a pacientului şi a factorilor de risc cardiovasculari la prezentare şi pe parcursul tratamentului antineoplazic, pre­cum şi evaluarea paraclinică prin efectuarea de rutină a electrocardiogramei şi a ecocardiografiei Doppler, cu de­ter­minarea FEVS.

Tratamentul efectelor secundare cardiovasculare tre­buie să fie rezultatul eforturilor medicului oncolog şi ale me­dicului cardiolog, care trebuie să desfăşoare gastric cancer unmet needs gastric cancer unmet needs în echipă, având ca obiectiv final îmbunătăţirea speranţei de viaţă a pacientului, astfel încât să putem trata cancerul protejând inima sau să se trateze inima permiţându-i pacientului cel mai bun tratament oncologic posibil.

Cuvinte-cheie: terapie anticancer, cardiotoxicitate, efecte secundare cardiovasculare Introduction Cardiac disease and cancer are by far the two most common disease conditions in the developed world. Cancer therapy is more effective than ever before at treating cancer, but has a price. Cardiotoxi­ city is a significant adverse effect of cancer treatment, gastric cancer unmet needs responsible for increased morbidity and mortality.

The most frequent and serious effect of chemotherapeutic agents on the cardiovascular system is heart failure 8 with ventricular systolic dysfunction. Other toxic effects include hypertension, thromboembolic disease, pericardial disease, arrhythmias and myocardial ischemia. In childhood cancer survivors cardiac mortality is increased eightfold. Importantly, not all cardiovascular symptoms in patients treated for cancer are iatrogenic and the differential diagnosis should include co-morbid conditions or the adverse effects of other medications.

The awareness of the cardiovascular risks of cancer treatment may influence the choice of treatment strategy and optimize delivery of therapy. Additionally, this knowledge may also allow for timely interventions, such as life-style changes or treatment of subclinical disease, which gastric cancer unmet needs decrease potential harmful effects.

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Chemotherapeutic agents and molecular targeted therapies can injure the cardiovascular system at central level by deteriorating the heart function or in the periphery by enhancing hemodynamic flow alterations and thrombotic events often latently present in oncology patients.

Non-reversible or reversible: a cardinal distinction Historically, non-reversible cardiovascular side effects that eventually led to progressive cardiac disease were the consequence of some oncologic therapies; a prime example being anthracycline-induced cardiotoxicity leading to progressive systolic heart failure.

With the introduction of new cancer drugs, such as signalling inhibitors, a new phenomenon has been observed: cardiac dysfunction that resolves for most patients over time. In an effort to classify cardiotoxicity of cancer drugs, Ewer proposed a system to identify drugs that have the potential to cause irreversible damage Type I vs. However, this classification system does have limitations; for example, trastuzumab, a Type II drug, can trigger irreversible cardiac damage in patients with severe preexisting cardiac disease, or potentiate anthracycline Type I cardiotoxicity.

Supliment II JTMR

For cardiovascular side effects from other modern cancer therapeutics, such as angiogenesis inhibitors-induced arterial hypertension and nephrotoxicity, the reversibility remains unknown. Cardiac dysfunction and heart failure Cardiac dysfunction and heart failure are among the most serious cardiovascular side effects of systemic cancer treatment.

Conventional chemotherapeutics, such as anthracyclines, anti-metabolites, and cyclophosphamide, can induce permanent myocardial cell injury - albeit by hpv impfung fur jungen risiken mechanisms - and by cardiac remodeling. Understanding the mechanistic pathophysiology of cancer drug-associated cardiac dysfunction is important to predict, treat, and prevent these side effects, although it can be challenging to identify the proper mechanism in individual patients.

Data from endomyocardial biopsy and troponin I measurements suggest that myocyte injury may occur during or early after anthracycline exposure. However, due to substantial cardiac reserves and the activation of compensatory mechanisms, clinical manifestation may not become gastric cancer unmet needs until months to years after the initial chemotherapy exposure. Clinically, early cardiac side effects are typically reversible and self-limiting and include dysrhythmia, repolarization changes in the electrocardiogram, pericarditis, and less frequently myocarditis.

  1. Cu câteva decenii în urma, cercetătorii au stabilit că unele tipuri de cancere de piele nu arată și nu se răspândesc ca cele mai multe tipuri cunoscute de cancere de piele; aceste tipuri de cancer au fost în cele din urmă clasificate drept carcinoame cu celule Merkel.

It remains uncertain whether patients who experience these early cardiac side effects are also more likely to develop late anthracycline cardiotoxicity, a condition that leads to cardiomyopathy and systolic heart failure. Patients treated with anthracyclines are five times more likely to develop chronic heart failure or reduced left ventricular ejection fraction LVEF compared with those treated with a non-anthracycline-containing chemotherapy.

The incidence of anthracycline-induced cardiotoxicity is dose-dependent. Above this dosage, the rates of cardiotoxicity rise exponentially.

However, there is significant interindividual heterogeneity; patients over 65 years of age and children may develop toxicity at lower cumulative dosages.

Other factors that seem to influence sensitivity to anthracycline-induced cardiotoxicity include genetic predisposition, arterial hypertension, previous or concurrent mediastinal radiation therapy, and combination with alkylating or antimicrotubulechemotherapeutics; many other gastric cancer unmet needs factors have been studied, and from a practical standpoint we may assume gastric cancer unmet needs any insult that has previously damaged i.

Supliment II JTMR | Proteomics | Biomarker

It should be noted, however, that those risk factors that have been studied have had a relatively short follow-up period and long-term investigations are needed to better assess the true impact of risk factors for anthracycline cardiotoxicity. Several methods were investigated to reduce anthracycline cardiotoxicity, including pharmacokinetic modification by liposomal encapsulation, alteration of chemical structure leading to drugs such as epirubicin, altering drug-infusion regimens to decrease peak plasma levels, and attenuation of iron chelation through pre-treatment with dexrazoxane.

Most gastric cancer unmet needs these methods have been associated with a reduction in cardiovascular events in anthracycline-treated patients; however, except for the use of epirubicin, most of these strategies are not in common practice in the clinical setting.

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Other approaches to mitigate the cardiotoxic impact of anthracyclines employ potentially cardioprotective medications, gastric cancer unmet needs as angiotensin-converting enzyme ACE inhibitors. Although promising data have been published recently, convincing 9 supportive care evidence from large randomized and prospective trials is still needed. Other agents with myocyte destruction Any cancer drug that may lead to myocyte injury or destruction can induce irreversible cardiotoxicity. For example mitoxantrone, an anthracyclineanalogue, can result in cardiotoxicity that is not clinically different from the cardiac damage caused by true anthracyclines.

Cyclophosphamide can cause haemorrhagic cell necrosis that is more common with larger single doses, and may lead to severe heart failure or death. However, with the lower cycle doses presently used, these toxicities gastric cancer unmet needs seen infrequently.

Cisplatin has also been associated with late-onset cardiac dysfunction, although the cardiovascular side effects appear less severe than those of anthracyclines.

Finally, myocardial ischaemia induced by pyrimidine analogues infrequently leads to myocardial infarction with all long-term cardiovascular sequelae. Type II agents - myocardial dysfunction from agents not associated with cumulative dose-relate cardiotoxicity Gastric cancer unmet needs number of recently introduced cancer drugs cause cardiac dysfunction.

This incidence was much higher than that associated with anthracycline treatment alone. One common finding was that the concomitant use of trastuzumab with anthracycline greatly increased the gastric cancer unmet needs of cardiotoxicity.

Consequently, in all adjuvant breast cancer trials, trastuzumab was only used after anthracyclines or with anthracycline-free chemotherapy. This lowered the incidence of severe heart failure to Importantly, patients in these trials were carefully selected and were required to have a normal cardiac function i.

Further analysis of the time interval between the administration of the anthracycline and the start of trastuzumab suggested that a strong correlation in the concomitant administration was associated with the highest reported incidence of cardiotoxicity, while an interval of 3 months had an incidence that was almost as low as was the incidence for those who had not been treated with prior anthracyclines.

  • Bacteriile folosesc acest mecanism, numit sistem de secreție Tip IV T4SSpentru a injecta molecule toxice în celule și de asemenea pentru a răspândi genele care generează rezistența la antibiotice a bacteriilor.

This observation supported the concept that trastuzumab may well act as a modulator of anthracycline toxicity when administered during a period of myocyte vulnerability following anthracycline exposure.

One common finding in these trials was that cardiac dysfunction and heart failure occurred predominantly during the trastuzumab treatment and was frequently reversible. However, only data from about 5 years of the patient follow-up in the most prominent trastuzumab trials are available, and longer-term surveillance is needed. The cardiotoxicity of other anti-HER2 therapies, such as the small molecule tyrosine kinase TKI inhibitor lapatinib, look promising, however they are still under investigation.

Angiogenesis inhibitors anti-vascular endothelial growth factor cancer drugs Angiogenesis inhibitors that target VEGF with either antibodies against VEGF bevacizumab or small molecule TKIs sunitinib, sorafenib prolong the lives of patients with a variety of solid tumours. Vascular endothelial growth factor signaling also gastric cancer unmet needs a role in myocardial and vascular homeostasis, so it is not surprising that these drugs can affect endothelial cells, myocyte function, and metabolism.

Imuno-oncologia, un progres major in tratarea cancerului

Bevacizumab causes cardiac dysfunction and heart failure in 3. Two recent meta-analysis, including almost patients treated with sunitinib and patients treated with sorafenib showed a rate of 4. The pathophysiology of anti-VEGF-induced cardiac dysfunction and heart failure remains poorly understood.

Sunitinib can induce myocyte apoptosis in preclinical models: although, similar to trastuzumab, cardiac biopsies from patients treated with this agent show no major myocardial injury. Furthermore, all of these agents can induce arterial hypertension, which may lead to secondary heart failure in vulnerable patients.

Initial reports described severe heart failure in 10 CML patients treated with imatinib, but these findings could not be confirmed in a large followup study. Isolated events of heart failure were also reported in CML patients treated with dasatinib. Both compounds can also induce peripheral oedema, pleural and pericardial effusion unrelated to heart failure - a condition that has to be considered in the differential diagnosis.

On a dose-dependent basis, these drugs can worsen gastric cancer unmet needs hypertension, or can cause de novo hypertension to develop.

The mechanism of angiogenesis gastric cancer unmet needs hypertension is not completely understood, but may be directly linked to the inhibition of VEGF-2 signaling. Hypertension involves mechanisms gastric cancer unmet needs to those of tumor destruction, and therefore may also be a marker for efficacy of angiogenesis inhibitors. Vasospastic and thromboembolic ischaemia associated with anti-cancer treatment Among agents associated with coronary artery spasm, the pyrimidine analogues 5-fluorouracil 5-FU and its oral pre-drug capecitabine are the most common.

Nitroglycerin and calcium-channel blockers are often effective for the treatment and prevention of ischaemia. In rare instances, progression to myocardial infarction gastric cancer unmet needs been reported. Cisplatin Bevacizumab tamoxifen sunitinib and sorafenib showed increased incidences of thromboembolic events.

Dysrhythmia and QT prolongation Rhythm disturbances associated with anti-cancer treatment are typically transient and not especially troubling. They occur most commonly as a consequence of metabolic changes and generally resolve after electrolyte homeostasis is cancer in peritoneal lining. Anthracyclines cause supraventricular arrhythmias and ventricular ectopy, taxanes cause sinus bradycardia and QT prolongation is associated with a number of anti-cancer drugs and may constitute a significant problem.

Virtually all anticancer drugs impact the cardiovascular system one way or another!

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Cardiovascular evaluation of patients before treatment with anticancer agents All patients undergoing chemotherapy should have prior careful clinic evaluation and assessment of CV risk factors or comorbidities. Frequent vital signs monitoring is recommended during chemotherapeutic agent infusion, particularly with 5-FU or paclitaxel.

ECG and clinic cardiovascular evaluation are useful to screen signs of cardiomyopathy, conduction disturbances, QT interval, before beginning anticancer therapy with anthracycline or paclitaxel or small molecule TKIs.

Early detection of cardiotoxicity allows the treating oncologist to redirect therapy or dose modify, taking into account gastric cancer unmet needs cost of a reduction in therapy against the potential of further injury to the patient. In these instances, the role of the cardiologist is to assist and advise the oncologist by providing diagnostic and prognostic information regarding developing cardiotoxicity.

A patient who has a comorbidity of cardiovascular disease and cancer could possibly have a different outcome depending on whether he or she was first seen by an oncologist or a cardiologist.

The oncologist takes a tumor-centric perspective in diagnosis, and in the past might have been missing the incumbent cardiopathy of the individual.

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The cardiologist treats the cardiopathy correctly, but oxiuros symptoms not pick up early signs of cancer, thus the patient risks further progression and oncologic complications.

Gastric cancer unmet needs should improve patient life expectancy, treating cancer while protecting the heart, or treating the heart and providing a thorough oncologic check up. The patient is monitored throughout therapy and follow-up so that eventual cardiovascular alterations can be detected in a timely manner and treated either by intervention on the cardiovascular side or by modulation of the cancer therapy.

Gastric cancer unmet needs cooperation between cardiologists and oncologists is thus crucial in order to balance the risks and benefits of cardiotoxic anticancer therapy and the oncologist should be aware of the cardiotoxic potential of cancer therapies.

Yeh ET. Cardiotoxicity induced by chemotherapy and antibody therapy. Annu Rev Med ;— J ClinOncol ; — J ClinOncol ;— Hooning MJ.

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Jurcut R, Gastric cancer unmet needs Care Cancer ;— Nat ClinPractOncol ;— Suter T. Cancer drugs and the heart: importance and management European Heart Journal doi AJ ClinOncol ;— Circulation ;— Circulation — J ClinOncol — Eur Heart J — Altena R, et al.

Longitudinal changes in cardiac function after cisplatin-based chemotherapy for testicular cancer. Ann Oncol ;— Bang YJ, Lancet ;— Slamon D. N Engl J Med ;— Most of the weight gain happens during chemotherapy, 2 main mechanisms being behind this process: decreased metabolism and decreased ability to perceive satiety.

The decrease in metabolic rate happens because - besides the increased muscular catabolism generated by the decreased estrogen - the muscle mass is gradually lost through the sedentariness and inadequate intake of protein to sustain muscle mass.