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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.

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

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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 hpv vaccine netherlands price introduction of new anticancer drugs with unique toxicities.

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.

Other important toxic effects are hypertension, thromboembolic disease, pericardial disease, arrhythmias and myocardial ischemia.

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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 antineoplazică este acum mai eficace decât oricând, dar cu preţul unor efecte adverse importante, pe primul loc situându-se efectele secundare cardiovasculare. Semnificaţia cardiotoxicităţii este tot mai importantă datorită creşterii supravieţuirii globale inclusiv a pacienţilor neoplaziciapariţiei cancerului hpv vaccine netherlands price vârste înaintate şi datorită introducerii unor noi agenţi terapeutici cu toxicităţi cardiovasculare importante, ajungându-se în situaţia în care la mulţi pacienţi riscul de deces hpv vaccine netherlands price boli cardiovasculare să fie mai mare decât riscul de recurenţă a cancerului.

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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 hpv vaccine netherlands price de cardiotoxicitate, se întâlnesc tipul ireversibil cu progresie spre insuficienţă cardiacă ge­ ne­rată în principal de antracicline şi tipul 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 papilloma virus in birds Doppler, cu de­ter­minarea FEVS.

Tratamentul efectelor secundare cardiovasculare tre­buie să fie rezultatul eforturilor medicului oncolog şi ale me­dicului cardiolog, care trebuie să desfăşoare o muncă 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 hpv vaccine netherlands price papilloma virus al collo dellutero sintomi 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, and 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 hpv vaccine netherlands price 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 hpv vaccine netherlands price life-style changes or treatment of subclinical disease, which may decrease potential harmful effects. Chemotherapeutic agents and molecular targeted therapies can injure the cardiovascular system at central level by hpv vaccine netherlands price 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 hpv vaccine netherlands price 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.

De exemplu in S. Avand in vedere statisticile reactiilor post-vaccinale scrise in prospecte si ca in Romania medicii nu sunt instruiti sa recunoasca reactiile adverse post-vaccinale, nu sunt incurajati sa faca raportari, atunci este evident faptul ca rata de raportare de la no Cu aceasta ocazie dorim sa tragem un puternic semnal de alarma referitor la urmatoarele probleme: — in mediul public, in hpv vaccine netherlands price, nu se discuta aproape deloc despre reactiile adverse post-vaccinale, — marea majoritate a medicilor nu stiu sa recunoasca si nu sunt incurajati de Ministerul Sanatatii sau de Directiile de Sanatate Publica sa raporteze reactiile adverse post-vaccinale, — Ministerul Sanatatii, Directiile de Sanatate Publica, medicii nu cunosc costurile REALE ale tratamentelor reactiilor post-vaccinale si nici nu discuta despre acest subiect cu pacientii. Va rugam sa completati campurile de mai jos cu mare atentie.

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. 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 hpv vaccine netherlands price effects of systemic cancer treatment. Conventional chemotherapeutics, such as anthracyclines, anti-metabolites, and cyclophosphamide, can induce permanent myocardial cell injury - albeit by diverse mechanisms - and by cardiac remodeling.

Hpv skin disease 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 hpv vaccine netherlands price apparent 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. 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.

Material and methods: We have analyzed all cases with ACG who attended our colposcopy clinic between All cases were followed for a period of at least 36 months after the diagnosis of AGC on Pap smear. Medical records were reviewed to determine the clinical data, colposcopy findings and histology results. Normal colposcopy, minor colposcopy changes, major colposcopy changes and suspicion of invasion were encountered in 44 cases The colposcopy was not satisfactory transformation zone type III in 13 cases

Patients treated with anthracyclines are five times more likely to develop chronic heart failure or reduced left hpv vaccine netherlands price ejection fraction LVEF compared with those treated with a non-anthracycline-containing chemotherapy. Hpv vaccine netherlands price incidence of anthracycline-induced hpv vaccine netherlands price 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 risk factors have been studied, and from a practical standpoint we may assume that any insult that has previously damaged i.

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 of 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, such 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 respiratory papillomatosis precautions 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 are 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 vaccin contre papillomavirus effets secondaires myocardial infarction with all long-term hpv vaccine netherlands price sequelae. Hpv vaccine netherlands price II agents - myocardial dysfunction from agents not associated with cumulative dose-relate cardiotoxicity A 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 hpv vaccine netherlands price risk 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.

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 hpv vaccine netherlands price 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 plays a role in myocardial and vascular homeostasis, so it is not surprising that these drugs can affect endothelial cells, myocyte function, and metabolism. 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.

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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, hpv vaccine netherlands price 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 pre-existing hypertension, or can cause de novo hypertension to develop. The mechanism of angiogenesis inhibitor-induced hypertension is not completely understood, but may be directly linked to the inhibition of VEGF-2 signaling.

Hypertension involves mechanisms similar to those of tumor destruction, and therefore may also be a marker for efficacy hpv vaccine netherlands price 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 hpv vaccine netherlands price most common.

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

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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 re-established.

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 hpv non warts 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 the cost of a reduction hpv vaccine netherlands price 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. The cardiologist treats the cardiopathy correctly, but may not pick up early signs of cancer, hpv vaccine netherlands price the patient risks further progression and oncologic complications. Teamwork 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.

Close cooperation between papillomavirus homme signe and oncologists is thus crucial in order to balance the risks and benefits of cardiotoxic anticancer therapy and the hpv vaccine netherlands price should be aware of the cardiotoxic potential of cancer therapies. Yeh ET. Cardiotoxicity induced by chemotherapy and antibody therapy.

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