Targeted therapy in patients with radioiodine-refractory differentiated thyroid cancer (DTC)

Papillary (PTC) and follicular (FTC) thyroid cancer (TC) belong to differentiated thyroid cancer (DTC). The initial treatment of DTC is surgery followed by radioiodine remnant ablation. Although the prognosis of DTC is generally good, approximately 10-15% of DTC patients will devolp advanced disease and their disease will become radioiodine refractory. Even in radioiodine refractory patients the natural history of disease can be slowly progressive or indolent.The expanded knowledge of the the biological basis of DTC has opened new opportunities in therapy – targeted therapy, aimed at inhibiting specific molecular targets and pathways in tumor proliferation, survival and progression. We rewieved different tageted therapies in DTC. Sorafenib was the first and only targeted drug approved by FDA for progressive and radiodine-refractory DTC. Also, lenvatinib had promising efficacy results in phase III trial, probably even better than sorafenib, but with more treatment-related deaths. The timing of targeted therapy for DTC is of decisive importance. The potential benefit should be balanced with potential toxicity of targeted therapies

Camurati-Engelmann Disease in a Family from Croatian Island: An Old Bone Scan Confirmed Pattern of Inheritance

34-year old patient had history of muscular wasting, easy fatigability, pain in extremities and waddling gait since age of four. During the time, neuromuscular disease was suspected, but not confirmed. Elevated bone alkaline phosphatase as well as other bone turnover markers (osteocalcin, procollagen, telopeptide) indicated further skeletal evaluation. Symmetrical enhanced uptake on technetium methylene diphosphonate [99mTc]MPD bone scintigraphy at diaphyses of longitudinal bones and scull matched cortical thickening of long bones and sclerosis of the scull seen at radiograms. Those findings pointed to Camurati-Engelmann disease misdiagnosed for the long time. This rare genetic autosomal dominant disorder was retrospectively diagnosed in asymptomatic father too on the basis of bone scans done long time ago. Old family member scans confirmed heredity pattern of the disease

Camurati-Engelmann Disease in a Family from Croatian Island: An Old Bone Scan Confirmed Pattern of Inheritance

34-year old patient had history of muscular wasting, easy fatigability, pain in extremities and waddling gait since age of four. During the time, neuromuscular disease was suspected, but not confirmed. Elevated bone alkaline phosphatase as well as other bone turnover markers (osteocalcin, procollagen, telopeptide) indicated further skeletal evaluation. Symmetrical enhanced uptake on technetium methylene diphosphonate [99mTc]MPD bone scintigraphy at diaphyses of longitudinal bones and scull matched cortical thickening of long bones and sclerosis of the scull seen at radiograms. Those findings pointed to Camurati-Engelmann disease misdiagnosed for the long time. This rare genetic autosomal dominant disorder was retrospectively diagnosed in asymptomatic father too on the basis of bone scans done long time ago. Old family member scans confirmed heredity pattern of the disease

CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND FOLLOW-UP OF PATIENTS WITH MELANOMA

Učestalost melanoma u zapadnom je svijetu u znatnom porastu. Jedan od važnijih čimbenika tog porasta jest sporadično, nekontrolirano izlaganje suncu. Temelj liječenja primarnog melanoma jest kirurško liječenje. Liječenje metastatske bolesti posljednjih godina doživljava znatne promjene. Inhibitori BRAF-a i MEK-a, imunoterapija inhibitorima receptora programirane stanične smrti (anti-PD-1-protutijela) nove su terapijske opcije za liječenje metastatske bolesti. Multidisciplinarni tim Hrvatskog društva za internističku onkologiju HLZ-a donosi preporuke za dijagnostiku, liječenje i praćenje melanoma, ponukan prije svega otkrićem novih lijekova i terapijskih mogućnosti, koji mijenjaju prognozu bolesnika s metastazama melanoma.Melanoma in the Western world has an increasing incidence. One of the most important factor for the increase in incidence is sporadic, uncontrolled exposure to the sun. The basis for the treatment of primary melanoma is surgical treatment. Treatment of metastatic disease of melanoma in recent years experienced significant changes. BRAF and MEK inhibitors, immunotherapy with programmed cell-death immune checkpoint inhibitors (anti-PD-1-antibodies) are new ­options for the treatment of metastatic disease. A mulitidisiplinary team of Croatian Society for Medical Oncology provides recommendations for diagnosis, treatment and follow-up of melanoma primarily driven to the discovery of new drugs and therapeutic options, that change the prognosis of patients with metastatic melanoma

GUIDELINES FOR USAGE OF DIAGNOSTIC PROCEDURES PRIOR TO INITIATION OF ANTINEOPLASTIC TREATMENT – CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL RECOMMENDATIONS Part II. breast cancer, gynaecological malignancies (ovarial cancer, uterine cancer, cervical cancer), lung cancer, malignant melanoma, sarkomas, central nervous system tumors, head and neck cancer

Rak je drugi najvažniji uzrok smrti u našoj zemlji, odmah nakon bolesti srca i krvnih žila. S pretpostavkom porasta incidencije i smrtnosti od raka u idućim godinama, projekcije su da će se znatno povisiti troškovi dija-gnostike i liječenja raka, i zbog uvođenja novih dijagnostičkih tehnika i zbog inovativnih lijekova te metoda liječenja. Posljedično se nameće imperativ što boljeg iskorištavanja financijskih sredstava, raspoloživog osob-lja i tehnike, a sve radi osiguranja kontinuiteta prikladne dijagnostike i liječenja. Optimalnim provođenjem dijagnostičkih metoda mogu se spriječiti nepotrebno odugovlačenje obrade, rasipanje financijskih sredstava i nepotrebno opterećenje zdravstvenih djelatnika te skratiti liste čekanja. HDIO je donio ove smjernice radi prevladavanja navedenih problema, vodeći brigu o najvećoj koristi za bolesnika, što bi na kraju trebalo dovesti do racionalizacije i standardizacije dijagnostičkih postupaka u svakodnevnoj kliničkoj praksi. Smjernice bi trebale pomoći da iz cijele palete dijagnostičkih postupaka koji su nam na raspolaganju odaberemo najrelevan-tnije za pojedino sijelo i kliničku proširenost bolesti.Cancer is the second most important cause of death in our country, immediately after cardiovascular diseases. With the assumption that cancer incidence and mortality will increase in the next years, projections show that the costs of diagnosis and treatment of cancer will be significantly increased, both due to the introduction of new diagnostic techniques and innovative medicines and treatment methods. Consequently, the imperative of making optimal use of financial resources, available personnel and techniques is all the more necessary in or-der to ensure the continuity of adequate diagnosis and treatment. Optimal use of diagnostic methods can pre-vent unnecessary processing delay, waste of financial resources and unnecessary burden on healthcare work-ers, and shorten waiting lists. HDIO has made these guidelines with the aim of overcoming these problems, rationalizing and standardizing diagnostic procedures in everyday clinical practice. These guidelines should help us to select, from the entire range of diagnostic procedures available, those which are most relevant to a particular localization and clinical extension of the disease

Smjernice za provođenje dijagnostičkih pretraga prije početka liječenja onkološkog bolesnika – kliničke preporuke Hrvatskog društva za internističku onkologiju HLZ-a I. dio: tumori urogenitalnog sustava (rak bubrega, rak mokraćnog mjehura, rak prostate, rak testisa), tumori probavnog sustava (rak jednjaka, rak želuca, rak debelog i završnog crijeva, rak gušterače, rak žučnih vodova, hepatocelularni rak, neuroendokrine novotvorine) [Guidelines for usage of diagnostic procedures prior to initiation of antineoplastic treatment – Croatian society for medical oncology clinical recommendations Part I. tumors of urogenital system (renal cell cancer, urinary bladder cancer, prostatic cancer, testicular cancer), tumors of gastrointestinal system (oesophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, biliary ducts cancer, hepatocellular cancer, neuroendocrine neoplasms)]

Cancer is the second most important cause of death in our country, immediately after cardiovascular diseases. With the assumption that cancer incidence and mortality will increase in the next years, projections show that the costs of diagnosis and treatment of cancer will be significantly increased, both due to the introduction of new diagnostic techniques and innovative medicines and treatment methods. Consequently, the imperative of making optimal use of financial resources, available personnel and techniques is all the more necessary in or-der to ensure the continuity of adequate diagnosis and treatment. Optimal use of diagnostic methods can pre-vent unnecessary processing delay, waste of financial resources and unnecessary burden on healthcare work-ers, and shorten waiting lists. HDIO has made these guidelines with the aim of overcoming these problems, rationalizing and standardizing diagnostic procedures in everyday clinical practice. Guidelines should help us to select, from the entire range of diagnostic procedures available, those which are most relevant to a particular localization and clinical extension of the disease

Kliničko značenje urokinaznog aktivatora plazminogena i njegovog inhibitora PAI-1 u bolesnika s diferenciranim karcinomom štitnjače

Higher levels of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) are linked to the poor prognosis in a variety of malignances. Aim of the present study was to investigate the expression and clinical relevance of uPA and PAI-1 in differentiated thyroid cancer. Patients and methods: Analysis prospectively included 128 patients with thyroid tumors, among them 105 patients with differentiated thyroid carcinoma, 2 patients with anaplastic carcinoma and 21 patient with thyroid adenoma, who underwent surgery between 2002. and 2008. uPA and PAI-1 in paired cytosol samples of thyroid tumor and normal tissue were determined using enzyme-linked immunosorbent assay and correlated to the known prognostic features. Results: Both uPA and PAI-1 concentrations were significantly higher in differentiated thyroid tumors (uPA = 0.509±0.767 and PAI-1 = 6.337±6.415 ng/mg protein) than in normal tissue (uPA = 0.237±0.051, P<0.001 and PAI-1 =2.368 ±0.418 ng/mg protein, P<0,001) with positive correlation of the two proteins in the tumors (Pearson r=0.817, Spearman ρ=0.475, P<0.001). Both proteins’ concentrations were significantly different among various histological grades (uPA P =0.031 and PAI-1 P<0.001), showing higher values in higher tumor grades. uPA and PAI-1 were significantly higher if extrathyroidal invasion (uPA P=0.015, PAI-1 P <0.001) or distant metastases (PAI-1 P<0.001) had been present, and in tumors whose size exceeded 1 cm in diameter (uPA P=0.002 and PAI-1 P=0.001). Only uPA, but not PAI-1 was significantly higher in multicentric vs. solitary tumors (P=0.015). The differences of uPA and PAI-1 did not reach the significant level when patients with differentiated tumors below and above 40 years of age had been compared and in lymph node positive tumors compared to lymph node negative tumors. Survival analysis revealed the significant impact of both uPA and PAI-1 on the Progression-Free Survival (PFS) (82.22 vs. 49.478 months for patients with low and high uPA, respectively, P < 0.001; 8.068 vs. 44.964 months for patients with low and high PAI-1, respectively, P<0.001). Univariate analysis showed that sex (P= 0.025), tumor size (P<0.001), gradus (P<0.001), extrathyroid invasion (P<0.001), local lymph nodes involvement (P<0.001), distant metastases (P<0.001), uPA (P<0.001) and PAI-1 (P<0.001) were significant predictors of PFS, whereas age (P=0.56), histopathological variant (P= 0.206), and multifocality (P= 0.365) were not. Multivariate analysis confirmed that distant metastases (P = 0.037), tumor tissue uPA (P= 0.009), and PAI-1 (P= 0,06) were strong independent predictors of PFS in patients with differentiated thyroid carcinoma. Conclusion: The correlation of high uPA and PAI-1 with the known prognostic factors of poorer outcome and with lower PFS rate in patients with differentiated thyroid cancers proved that these proteins could be an additional prognostic parameter

Camurati-Engelmann disease in a family from Croatian Island: an old bone scan confirmed pattern of inheritance [Camurati-Englemannova bolest u obitelji s Hrvatskog otoka: stara snimka kostiju potvrdila je obrazac nasljeđivanja]

34-year old patient had history of muscular wasting, easy fatigability, pain in extremities and waddling gait since age of four. During the time, neuromuscular disease was suspected, but not confirmed. Elevated bone alkaline phosphatase as well as other bone turnover markers (osteocalcin, procollagen, telopeptide) indicated further skeletal evaluation. Symmetrical enhanced uptake on technetium methylene diphosphonate [99mTc]MPD bone scintigraphy at diaphyses of longitudinal bones and scull matched cortical thickening of long bones and sclerosis of the scull seen at radiograms. Those findings pointed to Camurati-Engelmann disease misdiagnosed for the long time. This rare genetic autosomal dominant disorder was retrospectively diagnosed in asymptomatic father too on the basis of bone scans done long time ago. Old family member scans confirmed heredity pattern of the disease

Camurati-Englemannova bolest u obitelji s Hrvatskog otoka: stara snimka kostiju potvrdila je obrazac nasljeđivanja

34-year old patient had history of muscular wasting, easy fatigability, pain in extremities and waddling gait since age of four. During the time, neuromuscular disease was suspected, but not confirmed. Elevated bone alkaline phosphatase as well as other bone turnover markers (osteocalcin, procollagen, telopeptide) indicated further skeletal evaluation. Symmetrical enhanced uptake on technetium methylene diphosphonate [99mTc]MPD bone scintigraphy at diaphyses of longitudinal bones and scull matched cortical thickening of long bones and sclerosis of the scull seen at radiograms. Those findings pointed to Camurati-Engelmann disease misdiagnosed for the long time. This rare genetic autosomal dominant disorder was retrospectively diagnosed in asymptomatic father too on the basis of bone scans done long time ago. Old family member scans confirmed heredity pattern of the disease.34-godišnji bolesnik od svoje četvrte godine u povijesti bolesti navodi mišićnu slabost, učestalo umaranje, bolove u rukama i nogama te gegajući hod. Niz godina obrađivan je zbog sumnje na neuromuskularnu bolest koja nije potvrđena. Povišena koštana alkalna fosfataza, kao i ostali markeri koštane pregradnje (osteokalcin, telopeptid, prokolagen) indicirali su obradu koštanog sustava. Scintigrafija kostiju sa [99mTc]MPD pokazala je simetrično pojačano nakupljanje u dugim kostima i na bazi lubanje što odgovara zadebljanju kortikalisa dugih kostiju i sklerozi baze lubanje prikazane na radiološkim snimkama. Snimke su ukazale na Camurati-Engelmannovu bolest čija je dijagnoza promakla dugo vremena. Radi se o rijetkoj genetskoj autosomno dominantnoj bolesti koja se kasnije dijagnosticirala i kod bolesnikova oca. Stare snimke člana obitelji potvrdile su nasljedni obrazac bolesti

Kliničke preporuke Hrvatskog društva za internističku onkologiju HLZ-a za dijagnozu, liječenje i praćenje bolesnika/ca oboljelih od melanoma kože [Croatian society for medical oncology clinical guidelines for diagnosis, treatment and follow-up of patients with melanoma]

Melanoma in the Western world has an increasing incidence. One of the most important factor for the increase in incidence is sporadic, uncontrolled exposure to the sun. The basis for the treatment of primary melanoma is surgical treatment. Treatment of metastatic disease of melanoma in recent years experienced significant changes. BRAF and MEK inhibitors, immunotherapy with programmed cell-death immune checkpoint inhibitors (anti-PD-1-antibodies) are new options for the treatment of metastatic disease. A mulitidisiplinary team of Croatian Society for Medical Oncology provides recommendations for diagnosis, treatment and follow-up of melanoma primarily driven to the discovery of new drugs and therapeutic options, that change the prognosis of patients with metastatic melanoma