Radioterapija infradijafragmalnih polja u bolesnika s limfomima: volumeni i nuspojave

Lymphomas are very radiosensitive and radiotherapy (RT) was the first treatment modality that enabled cure. It is the most effective single modality for local control of lymphomas. However, as a local form of treatment, curative intention is only possible if all lymphoma tissue can be incorporated in the volume to be irradiated with the prescribed total irradiation dose. That is why RT is a single modality only in early stage of nodular lymphocyte predominance Hodgkin’s lymphoma and low grade non-Hodgkin’s lymphoma. In most patients, RT can be used as consolidation therapy after chemotherapy or as salvage after failure of chemotherapy. In the past two decades, irradiation techniques have been improved in order to spare critical tissues and reduce toxicity. Although effective, RT is a neglected modality of treatment because of the appearance of new drugs and fear of side effects after irradiation. Radiation has been shown to be effective in the treatment of all stages and forms of lymphoma. Study data are still mostly derived from patients that received supradiaphragmal RT; therefore, there is no agreement about the best management approach in patients with infradiaphragmal lymphoma.Limfomi su vrlo radiosenzitivni pa je radioterapija (RT) bila prva metoda liječenja koja je omogućavala izliječenje. Ona je i dalje najučinkovitiji pojedinačni modalitet liječenja limfoma. Međutim, RT je lokalna terapija i kao jedini oblik liječenja dolazi u obzir ako je moguće sve tumorsko tkivo uključiti u volumen koji će se zračiti. Stoga se danas RT primjenjuje kao primarni modalitet liječenja samo u ranom stadiju nodularne limfocitne predominacije Hodgkinova limfoma i indolentnih ne-Hodgkinovih limfoma. U većine bolesnika RT je dio kombiniranog modaliteta liječenja kao konsolidacija nakon kemoterapijskog liječenja. Kod bolesnika u uznapredovalim stadijima bolesti RT se može primijeniti kao dio planiranog liječenja kada se RT aplicira na mjesta visokog rizika za recidiv te u slučajevima insuficijentnog odgovora na kemoterapiju. U protekla dva desetljeća tehnike zračenja su se promijenile te omogućavaju značajnije očuvanje rizičnih organa i smanjenje nuspojava. Iako učinkovita, RT je zanemaren modalitet liječenja zbog dostupnosti novih lijekova te zbog straha od nuspojava nakon zračenja. Zračenje je učinkovito u svim stadijima i oblicima limfoma. Dostupni podaci o učinkovitosti i nuspojavama RT odnose se na supradijafragmalna polja, zbog toga su potrebna istraživanja o najboljem RT pristupu liječenju bolesnika s infradijafragmalnom prezentacijom limfoma

Tumours of the Central Nervous System

U članku su izneseni epidemiološki podaci primarnih i metastatskih oblika tumora koji zahvaćaju SŽS. Preko nešto etioloških pojmova, te dijagnostike i kliničke slike dolazi se do programa liječenja i prognostičkih mogućnosti. Pri opisu postupaka liječenja polazi se od razvoja kemoterapije do novih strategija i angiogeneze kao mogućeg terapijskog cilja.In the article are presented epidemiogical data of primary and metastatic types of tumours occuring in the central nervous system. Through some etiological notions diagnostics and clinical features, the program of treatment and prognostic possibilities can be reached. In the description of treatment procedures the starting point is the development of chemotherapy leading to new strategies and angiogenesis as a possible therapeutic goal

High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options

HORMONAL THERAPY OF PROSTATE CANCER: ARE THERE ANY DILEMMAS LEFT?

Strategija liječenja bolesnika s adenokarcinomom prostate ovisi o procjeni proširenosti bolesti, procjeni rizika od povratka bolesti, dobi, očekivanom trajanju života, komorbiditetima, afinitetima i načinu života. Jedan od standardnih terapijskih modaliteta jest i hormonska terapija. Hormonska terapija raka prostate zapravo je terapija koja suprimira androgen (AST) ili koja terapija deprivira androgen (ADT). Njezinom primjenom dolazi do sniženja razine androgena u krvi, a kako su stanice adenokarcinoma najvećim dijelom (³80%) hormonski ovisne o androgenima, prestanak stimulacije stanica raka androgenima dovodi do njihove apoptoze, usporava se rast tumora i smanjuje se njegova veličina. Stoga se ta vrsta terapije rabi u liječenju karcinoma prostate. Hormonska terapija indicirana je kao prvi terapijski modalitet kod nalaza metastatske bolesti. U slučaju primjene radioterapije na prostatu zahvaćenu rakom s kurativnom namjerom (kod nemetastatske bolesti) preporučuje se primjena terapije koja deprivira androgen u bolesnika sa srednjim i visokim rizikom od povratka bolesti prije, za vrijeme i poslije radioterapije u trajanju od 6 mjeseci ili 2–3 godine ovisno o procijenjenom riziku od povratka bolesti. U vezi s primjenom terapije koja deprivira androgen, a koja se može primijeniti na više načina i u više kombinacija, za određene kliničke situacije ne postoje konačne preporuke. Razloga je više: premalen broj odgovarajućih kliničkih studija, heterogenost bolesnika u studijama što otežava interpretaciju podataka te nekonzistentni rezultati. Također, kako novije dijagnostičke metode i postupci omogućavaju ranije otkrivanje raka prostate, a ranije i sve uspješnije liječenje produžava život bolesnika s metastatskom bolešću, rezultati »ranijih« kliničkih studija mogu gubiti na aktualnosti. Isto tako, sa sve dužim preživljenjem bolesnika sve važnija postaje kvaliteta života, odnosno nuspojave liječenja, kao i procjena koristi u odnosu prema štetnosti same terapije. Cilj je prikaza da upozori na novije spoznaje, kao i na moguće dileme o mjestu i primjeni terapije koja deprivira androgen.The strategy for treating prostate cancer patients depends on the assessment of disease extent, assessment of the risk of disease relapse, assessment of life expectancy, comorbidities, affinities and life-style. Since the activity and survival of prostate cancer cells is at least initially dependent on androgen stimulation, hormonal therapy is one of the several standard treatment modalities. Hormonal therapy is aimed at decreasing this androgen stimulation either by lowering androgen production or by blocking receptor binding. Hormonal therapy is in fact androgen-suppressive therapy (AST) or androgen-deprivation therapy (ADT). If effective, it results in the lack of cancer cell stimulation, thus causing their apoptosis and consequently decline in tumor growth and size. Hormonal therapy is used as a first-line treatment modality for metastatic disease. In addition to this indication, hormonal therapy is also used as an adjunct to radiotherapy with curative intent for patients with non-metastic disease but having an intermediate and high risk of disease relapse. In combination with radiotherapy, hormonal therapy can be applied before, concomitantly and after radiotherapy for the duration of 6 months or 2 to 3 years depending on the risk estimation. Regarding hormonal therapy, it can be applied in combination with other treatments, in several ways, and sometimes there might be several options available. This possible lack of a specific recommendation is a consequence of the fact that there is a limited number of adequate clinical studies which, moreover, may have yielded inconsistent results sometimes simply due to the patients’ heterogeneity. Moreover, thanks to the newer and better diagnostic methods enabling the discovery of prostate cancer in earlier disease stages, as well as to the more effective treatments, there is also a prolongation of relapse-free survival and possibly of overall survival in patients having metastic disease. Consequently, the results of earlier clinical studies might no longer be applicable to the new »generations« of upcoming patients. As regards this improved survival, issues of patient’s quality of life and possible side-effects of hormonal therapy are also becoming increasingly relevant because hormonal adverse events are time-dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, this paper aims to give an overview of the more recent findings, indications and observations regarding hormonal therapy

LYMPHOMA DIAGNOSIS AND TREATMENT – SECOND CROATIAN CONSENSUS

Na sastanku održanom u ožujku 2012. godine na kojem su sudjelovali vodeći hrvatski stručnjaci donesene su nove, proširene i osuvremenjene preporuke o dijagnostici i liječenju limfoma. One obuhvaćaju morfološku, radiološku i nuklearnomedicinsku dijagnostiku, sustavno liječenje, radioterapiju i praćenje učinka liječenja najvećeg broja tumora limfocitne loze u odraslih osoba. Preporuke su donesene konsenzusom, na temelju izlaganja i prijedloga pojedinih stručnjaka koji su prvo raspravljeni unutar radnih skupina, a potom usuglašeni na plenarnom sastanku.New, extended and modernized recommendations for diagnostics and treatment of lymphomas were accepted at a meeting held in March 2012 with the participation of major Croatian experts. They encompass morphological, radiological and nuclear diagnostics, systemic treatment, radiotherapy and follow-up of most tumors of lymphoid tissues occurring in adults. The recommendations were agreed upon by consensus. Reporters presented data and suggested recommendations which had been first discussed in working groups and then agreed upon on the plenary session

MULTIPLE PRIMARY MALIGNANCIES

Multipli primarni tumori koji se javljaju kod istog bolesnika, metakrono ili sinkrono, relativno su rijedak događaj s porastom učestalosti posljednjih desetljeća. Cilj je ovog istraživanja utvrditi njihovu učestalost kod bolesnika liječenih hospitalno u Zavodu za radioterapijsku onkologiju Klinike za onkologiju Medicinskog fakulteta Sveučilišta u Zagrebu, KBC Zagreb u periodu od 2003. do 2009. godine. Učestalost je multiplih malignih tumora u navedenom periodu bila 2,4%. Od ukupno 103 bolesnika 97 je imalo dva, a 6 tri primarna tumora. Metakronih je tumora bilo 88, a sinkronih 20. Učestalost im je bila veća kod žena nego kod muškaraca, a i pojavljivali su se ranije kod žena nego kod muškaraca. Najčešće su kombinacije prvog i drugoga metakronog tumora kod muškaraca bile: rak prostate-maligni tumor probavnog sustava (osobito rak rektuma i debelog crijeva) i obrnutim redoslijedom te hematološke zloćudne bolesti-maligni tumor probavnog sustava; a kod žena: rak dojke-rak kontralateralne dojke i hematološke zloćudne bolesti (osobito ne-Hodgkinov limfom)-rak dojke. Valja očekivati da će učestalost bolesnika s višestrukim primarnim tumorima rasti, i zbog programa ranog otkrivanja tumora i zbog uspješnijeg liječenja i dužeg očekivanog trajanja života.Multiple primary malignancies, metachronous or synchronous, in a single patient are relatively rare event with the increase of incidence in recent decades. The aim of this research is to study their incidence in patients hospitalized at the Division of Radiotherapy, Department of Oncology, University of Zagreb, School of medicine, University Hospital Centre Zagreb from 2003 to 2009. The incidence of multiple primary malignancies was 2.4%. Among 103 patients, 97 had two, and 6 three primary tumors. Eighty-three cases were metachronous, while 20 cases were synchronous malignancies. The frequency was higher in females than males and their age at diagnosis of tumors was younger than in males. The most common tumor combinations in males were: prostate cancer-digestive system malignancy (especially colorectal cancer) and viceversa, and hematological malignant tumors-digestive system malignancy; while in women there were: breast cancer-cancer of contralateral breast and hematological malignant tumors (especially lymphoma non Hodgkin)-breast cancer. The incidence of multiple primary malignancies is expected to increase due to the better screening programs for early detection of malignancies as well as considerable improvement in their treatment and longer life expectancy

High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin’s lymphoma

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options

Giant low-grade primary myofibroblastic sarcoma of the posterior chest wall

Primary myofibroblastic sarcoma is an extremely rare, highly malignant neoplasm, and only few cases had been reported in the literature worldwide. In the present study, we report an unusual case of a low-grade myofibroblastic sarcoma located in the posterior chest wall with intrathoracic propagation and discuss its clinical and pathological features

Adjuvant therapy after radical surgery of cervical cancer: Zagreb experience

The results of the analysis of the treatment of 72 patients with carcinoma of the uterine cervix are presented. Seventy-two patients with Stage IB1 carcinoma of the cervix underwent a radical hysterectomy and pelvic lymphadenectomy. The low-risk group includes the patients without unfavourable prognostic factors that were treated by surgery alone. The high-risk group included women with pelvic node metastases, clinical tumour size greater than 3.0 cm, depth of stromal invasion greater than 1/3 of the cervical wall, Grade 3 tumours and the presence of lympho-vascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks following surgery. Thirty-four patients (47.2%) were in the low-risk group and thirty-eight patients (52.8%) were in the high-risk group. Locoregional recurrences were diagnosed in three cases (8.8%) in the surgery group and in four patients (10.5 %) assigned to postoperative radiotherapy. The incidence of distant metastases was 2.9% in the group treated by surgery alone and 5.3% in the group treated by surgery and radiotherapy. Overall survival at five years was 91.2% in the low-risk group and 89.5% in the high-risk group of patients. Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, which emphasizes the value of whole pelvic radiation in patients with one or more unfavourable prognostic factors after radical surgery in Stage IB1 cervical cancer