Najnoviji stavovi o prednostima primjene neoadjuvantne terapije kod pacijenata s uznapredovalim rakom želuca

Treatment for gastric cancer has multiple approaches and options across the world. Standard treatment for the Asian population comprises D2-gastrectomy and adjuvant chemotherapy. However, in Europe and North America, clinical trials have shown that perioperative chemotherapy, given to patients before surgery, could improve resection and survival rates significantly. Most recent studies have also discussed the advantages of doublet vs. triplet chemotherapy regimens. Furthermore, researchers have been comparing the effects of perioperative chemoradiotherapy as opposed to chemotherapy alone. The specific advantages of previously stated therapy options, as well as any novel treatments, should be researched more thoroughly in the future.Liječenje raka želuca ima više terapijskih pristupa i opcija diljem svijeta. Za azijsku populaciju standardna terapija uključuje D2 gastrektomiju s adjuvantnom kemoterapijom. Međutim, klinička ispitivanja u Europi i Sjevernoj Americi pokazala su da preoperativna kemoterapija, koja se daje pacijentima prije operacije, može značajno poboljšati R0 resekciju i stope preživljavanja. Najnovije studije također raspravljaju o prednostima dvostrukog naspram trostrukog režima kemoterapije. Nadalje, istraživači uspoređuju učinke preoperativne kemoradioterapije u odnosu na samu kemoterapiju. Specifične prednosti prethodno navedenih terapijskih opcija, kao i eventualni novi načini liječenja, trebalo bi detaljnije istražiti u budućnosti

Novosti u imunoterapiji melanoma

Melanoma is considered to be the most immunogenic malignant tumour. This fact is recognized for many years, and certain forms of immunotherapy have been used in melanoma therapy for a considerable time. Treatment options for patients with metastatic melanoma have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents (immunotherapies and targeted therapies). During this period, melanoma immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic Tlymphocyteassociated antigen4 (CTLA4) and, recently, the programmed cell-death protein 1 (PD1) immune checkpoints. These changes in the treatment options have dramatically improved patient outcomes, with the median overall survival of patients with metastatic melanoma increasing from approximately 9 months before 2011 to at least 2 years, and probably longer. Various types of immunotherapy, like pembrolizumab, nivolumab, ipilimumab, combined therapy with nivolumab and ipilimumab, and T-VEC, have been established in recent years as the standard-of-care treatment for metastatic melanoma patients.Melanomi se smatraju najimunogenijim zloćudnim tumorima. Ova je činjenica prepoznata već niz godina, te se neki oblici imunoterapije već dugo primjenjuju u liječenju melanoma. Terapijske opcije za liječenje bolesnika s metastatskim melanomom dramatično su se promijenile u zadnjih pet godina, te je Američka agencija za lijekove (FDA) odobrila osam novih lijekova (imunoterapije i ciljane terapije). Tijekom ovog razdoblja, imunoterapija melanoma promijenila se iz terapije bazirane na citokinima u protutijelima posredovanu blokadu citotoksičnog T-limfocitnog antigena 4 (CTLA-4), a u zadnje vrijeme u protutijelima posredovanu inhibiciju imunoloških kontrolnih točaka, prvenstveno proteina programirane stanične smrti 1 (PD-1). Ove su promjene terapijskih opcija dramatično poboljšale ishod liječenja bolesnika, te se medijan ukupnog preživljenja kod bolesnika s metastatskim melanomom povisio s približno 9 mjeseci prije 2011. godine, na najmanje 2 godine, a vjerojatno i dulje. Različiti oblici imunoterapije, poput pembrolizumaba, nivolumaba, ipilimumaba, kombinirane terapije nivolumabom i ipilimumabom, te T-VEC, postali su zadnjih godina standardni oblici liječenja bolesnika s metastatskim melanomom

Novosti u imunoterapiji melanoma

Melanoma is considered to be the most immunogenic malignant tumour. This fact is recognized for many years, and certain forms of immunotherapy have been used in melanoma therapy for a considerable time. Treatment options for patients with metastatic melanoma have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents (immunotherapies and targeted therapies). During this period, melanoma immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic Tlymphocyteassociated antigen4 (CTLA4) and, recently, the programmed cell-death protein 1 (PD1) immune checkpoints. These changes in the treatment options have dramatically improved patient outcomes, with the median overall survival of patients with metastatic melanoma increasing from approximately 9 months before 2011 to at least 2 years, and probably longer. Various types of immunotherapy, like pembrolizumab, nivolumab, ipilimumab, combined therapy with nivolumab and ipilimumab, and T-VEC, have been established in recent years as the standard-of-care treatment for metastatic melanoma patients.Melanomi se smatraju najimunogenijim zloćudnim tumorima. Ova je činjenica prepoznata već niz godina, te se neki oblici imunoterapije već dugo primjenjuju u liječenju melanoma. Terapijske opcije za liječenje bolesnika s metastatskim melanomom dramatično su se promijenile u zadnjih pet godina, te je Američka agencija za lijekove (FDA) odobrila osam novih lijekova (imunoterapije i ciljane terapije). Tijekom ovog razdoblja, imunoterapija melanoma promijenila se iz terapije bazirane na citokinima u protutijelima posredovanu blokadu citotoksičnog T-limfocitnog antigena 4 (CTLA-4), a u zadnje vrijeme u protutijelima posredovanu inhibiciju imunoloških kontrolnih točaka, prvenstveno proteina programirane stanične smrti 1 (PD-1). Ove su promjene terapijskih opcija dramatično poboljšale ishod liječenja bolesnika, te se medijan ukupnog preživljenja kod bolesnika s metastatskim melanomom povisio s približno 9 mjeseci prije 2011. godine, na najmanje 2 godine, a vjerojatno i dulje. Različiti oblici imunoterapije, poput pembrolizumaba, nivolumaba, ipilimumaba, kombinirane terapije nivolumabom i ipilimumabom, te T-VEC, postali su zadnjih godina standardni oblici liječenja bolesnika s metastatskim melanomom

Quality of Life in Croatian Metastatic Melanoma Patients

The aim of this study was to examine the quality of life (QoL) in 40 Croatian metastatic melanoma patients who had completed at least first-line treatment and to see if there was a correlation between QoL parameters and serum lactate dehydrogenase (LDH). LDH levels were measured and all patients clinically examined between April and September 2013. Two QoL questionnaires were used for patient self-evaluation: the European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC QLQ-C30) and the Dartmouth Primary Care Cooperative Research Network and the World Organization of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians (COOP/WONCA) charts. The average EORTC QLQ-C30 score for global health status (GHS) was 41.204. The average scores for functional scales were high, with the exception of emotional functioning (65.02). Blood LDH levels positively correlated with the Eastern Cooperative Oncology Group (ECOG) status (r=0.415; p<0.01) and pain (r=0.345; p<0.05), but not with any functional or COOP/WONCA scores. Global health status (GHS) positively correlated with patient age at the time of evaluation (r=0.386; p<0.05) and age at the time when metastatic disease had been diagnosed (r=0.366; p<0.05). Quality of life for the studied group of metastatic melanoma patients in Croatia can be considered generally good, with the exception of emotional functioning and symptoms of fatigue, dispnoea, insomnia, and financial difficulties

Quality of Life in Croatian Metastatic Melanoma Patients

The aim of this study was to examine the quality of life (QoL) in 40 Croatian metastatic melanoma patients who had completed at least first-line treatment and to see if there was a correlation between QoL parameters and serum lactate dehydrogenase (LDH). LDH levels were measured and all patients clinically examined between April and September 2013. Two QoL questionnaires were used for patient self-evaluation: the European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC QLQ-C30) and the Dartmouth Primary Care Cooperative Research Network and the World Organization of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians (COOP/WONCA) charts. The average EORTC QLQ-C30 score for global health status (GHS) was 41.204. The average scores for functional scales were high, with the exception of emotional functioning (65.02). Blood LDH levels positively correlated with the Eastern Cooperative Oncology Group (ECOG) status (r=0.415; p<0.01) and pain (r=0.345; p<0.05), but not with any functional or COOP/WONCA scores. Global health status (GHS) positively correlated with patient age at the time of evaluation (r=0.386; p<0.05) and age at the time when metastatic disease had been diagnosed (r=0.366; p<0.05). Quality of life for the studied group of metastatic melanoma patients in Croatia can be considered generally good, with the exception of emotional functioning and symptoms of fatigue, dispnoea, insomnia, and financial difficulties

Uncovering the Connection Between Stress and Cancer: A Case Report

Many research studies show the connection between a previous stressful event and an increase in health problems. These usually include heart disease, diabetes, and hypertension. However, whether this could affect the immune system and be a trigger for developing carcinoma remains open for discussion

Liječenje kolorektalnog raka: uvodnik

Colorectal cancer (CRC) is one of the most frequent type of cancers, and also one of the most frequent causes of death among cancer patients worldwide. Approximately 25% of newly diagnosed patients with CRC have already developed metastases, and 50% of all CRC patients will develop metastases over time as the disease progresses. Active oncological treatment of patients having metastatic CRC nowadays includes fluoropyrimidines in combination with irinotecan and/or oxaliplatin ± monoclonal antibodies (mAbs). Development and introduction of monoclonal antibodies targeting the vascular endothelial growth factor (VEGF; bevacizumab) and the epidermal growth factor receptor (EGFR; cetuximab, panitumumab) in treatment algorithms for patients with wild-type K/N-RAS have significantly improved median overall survival (OS) of patients with metastatic colorectal cancer. Clinical experience supported by various patohistological and molecular biology data indicates that CRC is a heterogeneous disease. The novel approach to treatment decisions should be patient personalized, i.e. such decisions should be tailored according to patient clinical (age, performance status, comorbidities) and molecular (pharmacogenetic) characteristics, tumor disease stage, tumor location and tumor molecular characteristics and patient preferences. Treatment decision for patients with metastatic CRC must be evidence based. The role of the multidisciplinary team in recommendation preparation is unavoidable.Rak debelog crijeva (CRC) jedan je od najčešćih vrsta raka, a također i jedan od najčešćih uzroka smrti kod pacijenata oboljelih od raka u svijetu. Oko 25% novodijagnosticiranih bolesnika s CRC u trenutnku postavaljnja dijagnoze već je razvilo metastaze, a 50% svih bolesnika s kolorektalnim karcinomom razviti će metastaze s vremenom kako bolest napreduje. Aktivno onkološko liječenje pacijenata s metastatskim CRC bazira se na fluoropirimidinima (5FU) u kombinaciji s irinotekanom i / ili oksaliplatinom ± monoklonska protutijela (Mab). Razvoj i uvođenje monoklonskih antitijela usmjerenih na faktor rasta vaskularnog endotela (VEGF; bevacizumab) i receptor epidermalnog faktora rasta (EGFR; cetuksimab, panitumumab) u bolesnika s divljim tipom K/ N-RAS, u algoritam za liječenje, znatno je poboljšano prosječno preživljavanja (OS) bolesnika s metastatskim rakom debelog crijeva. Kliničko iskustvo, kao i patohistološki i molekularni podatci o biologiji tumora, pokazuju kako je CRC heterogena bolest. Novi pristup u liječenju mCRC treba biti individulano usmjeren na svakog pojedinog pacijenta, tj trebaju biti prilagođeni parametrima pacijenta (dob, klinički status, komorbiditeti) i parametrima tumora: stadiju bolesti, lokaciji tumora i molekularnim obilježljima tumora, te preferenciji pacijenta. Liječenje bolesnika s metastatskim CRC mora se temeljiti na dokazima i biti u skladu sa smjenicama stručnih društava. Uloga multidisciplinarnog tima u odluci o preporuci i provođenju terapije danas je mandatorna

Sustavna terapija raka debelog crijeva – pregled novih kliničkih studija

Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract worldwide, and also one of the leading causes of cancer-related mortality, accounting for more than 600000 deaths every year. Depending on the stage of the disease some patients who were surgically treated for CRC with curative intent require adjuvant chemotherapy (fluorouracile-based), which reduces the risk of recurrence and death in patients with stage III CRC, but its role in stage II is still controversial. Pathogenesis of CRC is a result of two different genetic pathways: chromosomal instability (CIN), and inactivation of mismatch repair (MMR) genes. Stage II patients with deficient MMR tumor status do not benefit from adjuvant therapy and should receive surgery alone. For patients with metastatic CRC optimal sequence of chemotherapy regimens and targeted therapy is still debated. Epidermal growth factor receptor (EGFR) has been validated as a therapeutic target in several human tumors including CRC. Recently it has been reported that activating mutations in exons 2, 3, and 4 of both KRAS and NRAS all predict a lack of response to EGFR trageted agents. Recent studies suggest BRAF is another prognostic and potential predictive biomarker of CRC. It is necessary to indentify new prognostic and predictive markers, to acquire maximal benefit from every therapy line and to improve prognosis of these patients.Rak debelog crijeva (CRC) najučestalija je maligna neoplazma gastrointestinalnog trakta, te je sa preko 600.000 smrti godišnje jedan od vodećih uzroka smrtnosti od zloćudnih bolesti. Ovisno o stadiju bolesti, neki od bolesnika koji su kirurški liječeni radi raka debelog crijeva s ciljem izlječenja zahtijevaju primjenu adjuvantne kemoterapije (bazirane na fluorouracilu) koja smanjuje rizik povrata bolesti i smrti u III. stadiju bolesti, no njena uloga u stadiju II još je uvijek nedovoljno jasna. Patogeneza u CRC rezultat je dvaju različitih molekulsko-genskih mehanizama: kromosomske nestabilnosti (CIN) te inaktivacije gena koji sudjeluju u popravku pogrešno spojenih fragmenata DNA (MMR). Na temelju provedenih istraživanja, u bolesnika stadija II u kojih je prisutan deficijentan MMR status ne postoji dobit od primjene adjuvantne terapije te je u toj skupini bolesnika kirurško liječenje dostatno. U bolesnika s metatastatskim CRC još uvijek nema konsenzusa o optimalnom redoslijedu kemoterapijskih protokola i ciljane biološke terapije. Receptor za epidermalni čimbenik rasta (EGFR) potvrđen je kao terapijski cilj u više humanih tumora, uključujući CRC. Odnedavno, istraživanja su pokazala da aktivirajuće mutacije na eksonima 2, 3 i 4 KRAS i NRAS gena dovode do izostanka odgovora na ciljanu terapiju usmjerenu na EGFR. BRAF je još jedan od istraživanih biljega u raku debelog crijeva, te je pokazano da je povezan sa lošijom prognozom. Potrebna su daljnja istraživanja i identifikacija novih prognostičkih i prediktivnih biljega kako bi se postigla maksimalna učinkovitost svake terapijske linije te poboljšala prognoza ovih bolesnika

Radiation Therapy in Treatment of Fibrodysplasia Ossificans Progressiva: A Case Report and Review of the Literature

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic disorder with diffuse extra-skeletal bone formation. The genetic mutation responsible for FOP has recently been discovered and is connected with excessive activation of bone morphogenetic protein receptor. This disease usually begins with typical ossification pattern in early childhood, causing increasing disability and making patients totally disabled by the age of 30. Ectopic ossification develops spontaneously and can be triggered by any trauma and even intramuscular injections. The symptoms of FOP are often misdiagnosed as cancer, causing unnecessary biopsies, which can precipitate further progressive heterotopic ossification. There is no effective treatment for this severe condition. Radiotherapy can be helpful in impeding ossification, although the strict evidence for that is lacking. There are only two reports in the literature referring to the use of radiotherapy in treatment of FOP. Herein, we present a 35-year-old patient successfully treated with small doses of fractionated radiotherapy in several courses. This case indicates that radiotherapy can be useful in treating patients with FO