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The 23rd Annual Congress of the Romanian Society for Radiotherapy and Medical Oncology (RSRMO)

“Modern approach in Oncology: from screening to state-of-the-art therapy”

Organized by:

Romanian Society for Radiotherapy and Medical Oncology

Institute of Oncology “Prof. Dr. Ion Chiricuţă” Cluj-Napoca

University of Medicine and Pharmacy “Iuliu Haţieganu” Cluj-Napoca

Grand Hotel Napoca, Cluj-Napoca, Romania

17 – 19 October 2013

Chair: Ovidiu CozaVioricaMagdalena Nagy

Tudor CiuleanuIoana Brie

Daniela Martin

Local Organizing Committee

Patriciu AchimasAlexandru IrimieClaudia OrdeanuNicolaeTodorMihaela Todor

Chair: Ovidiu CozaViorica Magdalena Nagy

Anca BojanRares Buiga

Florian NiculaOfelia Suteu

Ioana BrieDaniela Coza

Tudor CiuleanuDaniela Martin

Scientific Program Committee

Patriciu AchimasAlexandru IrimieAnca GrosuRichard PötterFerran GuedeaJulian MalickiDirk RadesClaudia OrdeanuAlin RanceaNicolaeTodor

The 23rd Annual Congress of the Romanian Society for Radiotherapy and Medical Oncology (RSRMO)

“Modern approach in Oncology: from screening to state-of-the-art therapy

SCIENTIFIC PROGRAMME

Journal of Radiotherapy & Medical Oncology, vol 19, 2013, Supplement 5

THURSDAY, 17 OCTOBER 2013

09:00 – 10:30 (VIENA HALL)Precongress course: „New discoveries in molecular targeted therapy 2013”Coordinator Assoc. Prof. Dr. T. E. Ciuleanu University of Medicine and Pharmacy „Iuliu Haţieganu” Cluj-Napoca

09:00 – 09:05Introducere Assoc. Prof. Dr. T. E. Ciuleanu

09:05 – 10:00Clasificarea ţintelor moleculare, update. Ce este deja autorizat FDA, EMA/ ANM?Dr. R. Curcă

10:00 – 10:15Celulele stem tumorale în cancerul colorectal – un nou marker?Dr. S. Şuşman

10.15 – 10.30 Rolul de biomarker al miARN în cancerul colorectal Dr. O. Bălăcescu

10:30 – 10:45 Coffee break


10:45 – 11:00Celulele tumorale circulante în cancerul colorectal – posibilităţi de detecţie şi implicaţii prognostice şi predictive Dr. R. Buiga

11:00 – 11:15Inflamazomii şi evaluarea profilului molecular al cancerelor Dr. Ioana Berindan Neagoe

11:15 – 11:30Markeri oncoimunologici şi posibilităţi de imunomodulare în cancerul colorectal Dr. N. Miron

11:30 – 11:50 Oncoimunologie – From bench to bedside – Bristol Myers Squibb SessionAssoc. Prof. Dr. T. E. Ciuleanu

11:50 - 12:20Actualităţi în terapia moleculară ţintită a tumorilor digestive Assoc. Prof. Dr. T. E. Ciuleanu

12:20 – 13:10 Lunch

6 Journal of Radiotherapy & Medical Oncology, vol 19, 2013, Supplement


13:10 – 13:55Actualităţi în terapia personalizată a cancerelor bronhopulmonare Assoc. Prof. Dr. T. E. Ciuleanu

13:55 – 14:40Interacţiunea tumoră-gazdă- o nouă ţintă pentru tratamentul personalizat al cancerului mamar?Dr. A. Eniu

14:40 – 15:10Actualităţi în terapia personalizată a altor tumori solideAssoc. Prof. Dr. T. E. Ciuleanu

15:10 – 15:25Take home messages Assoc. Prof. Dr. T. E. Ciuleanu

15:30 – 15:50 (ATENA HALL)Eli Lilly SymposiumAlimta (pemetrexed) - Innovative aspects in the management of advanced and metastatic non-small cell lung cancerAssoc. Prof. Dr. T. E. Ciuleanu


16:10 – 17:30 (ATENA HALL)

Resident afternoon Moderators: Prof. Dr. Viorica Nagy, Dr. O. CozaUniversity of Medicine and Pharmacy „Iuliu Haţieganu” Cluj-Napoca

17:30 – 17:50 Vifor Pharma SymposiumIntravenous iron and hematopoietic response: from clinical studies to clinical practiceAssoc. Prof. Dr. T. E. Ciuleanu

17:50 – 18:10 Teva Pharmaceuticals SymposiumEpisodic pain in oncology pacientsDr. R. Curca

18:10 – 18:30 Sandoz Pharma SymposiumImpact of chemotherapy-induced anaemia in cancer patientsAssoc. Prof. Dr. T. E. Ciuleanu

18:30 – 18:50 Merck Sharp&Dohme (MSD) SymposiumAprepitant – proven efficacy for the prevention of chemotherapy-induced nausea and vomiting (CINV) Dr. Larisa Ciule


18:50 – 19:10 AstraZeneca SymposiumTherapeutic options after PSA progression following initial hormonal therapy in advanced prostate cancerAssoc. Prof. Dr. T. E. Ciuleanu

19:30 – 22:00 WELCOME RECEPTION - Grand Hotel Napoca

FRIDAY, 18 OCTOBER 2013

08:45 – 09:00 (ATENA HALL)Opening CeremonyProf. Dr. A. Irimie – Rector of the University of Medicine and Pharmacy „Iuliu Haţieganu” Cluj-NapocaAssoc. Prof. Dr. Anca Bojan – Medical Director of the Institute of Oncology „Ion Chiricuţă” Cluj-NapocaDr. O. Coza – RSRMO President

09:00 – 10:20 Epidemiology SessionModerators: Assoc. Prof. Dr. Anca Bojan, Dr. F. Nicula

09:00 – 09:20Incidence of tyroid cancer in Cluj County, 1998-2009Dr. Ofelia Şuteu – University of Medicine and Pharmacy „Iuliu Haţieganu” Cluj-Napoca

09:20 – 09:40Cancer surveillance in North-Western region of Romania. Recent trends in major cancers incidence and mortality Dr. Daniela Coza – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

09:40 – 10:00The Oncology Institute „Prof. Dr. Ion Chiricuţă” Cancer prevention and control Department report on cancer control activitiesDr. F. Nicula – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

10:00 – 10:20 Significance of circulating tumor cells in cancer therapy managementDr. R. Buiga Potcoava – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca


10:40 – 12:30 (ATENA HALL)Diagnosis & New Technologies SessionModerators: Prof. Dr. Anca Grosu, Prof. Dr. Viorica Nagy

10:40 – 11:10Biological Imaging for Radiation Treatment PlanningProf. Dr. Anca Grosu – University Medical Center Freiburg, Germany


11:10 – 11:30Predictive assays in clinical oncologyDr. Ioana Brie – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

11:30 – 11:50Modern oncologic imagingDr. C. Popiţa – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

11:50 – 12:05Digital Breast Tomosynthesis in Breast Cancer Diagnosis and ScreeningDr. Carmen Lisencu – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

12:05 – 12:20 Development of a joint platform for research publishing in non-English speaking countries - presentation of „Reports of Practical Oncology and Radiotherapy Journal” Prof. Dr. J. Malicki – Greater Poland Cancer Center, Poznan, Poland

12:20 – 13:20 Lunch

12:20 – 12:50 Poster Session (I)

13:20 – 15:20 (ATENA HALL)Treatment Session (I)Moderators: Prof. Dr. R. Pötter, Dr. O. Coza

13:20 – 13:50Current concepts and clinical evidence in image guided adaptive brachytherapy of cervical cancer Prof. Dr. R. Pötter – Department of Radiotherapy, Comprehensive Cancer Centre, General Hospital Vienna, Medical University of Vienna, Austria

13:50 – 14:20Is SBRT the future of RT?Prof. Dr. F. Guedea – Catalan Institute of Oncology, University of Barcelona, Barcelona, Spain

14:20 – 14:50Presenting European Guidelines on a risk assessment and analysis of adverse events and near misses in radiotherapyProf. Dr. J. Malicki – Greater Poland Cancer Center, Poznan, Poland

14:50 – 15:20 Survival scores in palliative radiotherapyProf. Dr. D. Rades – University Hospital Schleswig-Holstein, Campus Lübeck, Germany

15:20 – 16:00 Place of hormonal therapy in advanced breast cancer – with AstraZeneca supportPlace of hormonal therapy in early breast cancer management Dr Alexandru Eniu, Romania Place of hormonal therapy in advanced breast cancer management Dr Meritxell Bellet, Spain



16:00 – 16:20 Poster Session (II)

16:20 – 17:10 (ATENA HALL) Janssen SymposiumModerator: Assoc. Prof. Dr. T. E. CiuleanuEnhancing Hormonal Therapies and Enzimatic Mechanism of Action in metastatic Castration Resistant Prostate Cancer with focus on Abiraterone Prof Dirk Schrijvers, Medische Oncologie Antwerpen, Belgium

17:10 – 17:30 Amgen SymposiumOptimizing chemotherapy in breast cancer patients: dealing with toxicityDr. A. Eniu, Dr. M. Dediu

17:30 – 17:50 GlaxoSmithKline (GSK) SymposiumNew evidence, new standards? Redefining treatment selection in mRCCDr. Larisa Ciule

18:00 – 19:30 The Annual 23rd RSRMO Congress Meeting - 2013 Annual Report - election for RSRMO Board of Directors 2014-2016

20:00 – 23:00 Dinner

SATURDAY, 19 OCTOBER 2013

09:00 – 10:20 (ATENA HALL)Treatment Session (II)Moderators: Assoc. Prof. Dr. Anca Bojan, Dr. O. Coza

09:00 – 09:20Myeloma management in the era of novel agentsAssoc. Prof. Dr. Anca Bojan – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

09:20 – 09:40 Neadjuvant chemotherapy in the treatment of cervical cancer advances and controversiesProf. Dr. Viorica Nagy – University of Medicine and Pharmacy „Iuliu Haţieganu” Cluj-Napoca

09:40 – 10:00TNF siRNA as modulators of apoptosis and angiogenesis, in cell migration and invasion in Triple Negative Breast Cancer Cells (TNBC)Dr. Ioana Berindan Neagoe – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

10:00 – 10:20Local experience in the clinical set-up of ultrasound-guided brachytherapy in cervix cancerDr. Claudia Ordeanu – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

10:20 – 10:40Risk factors and long term survival in germ cell tumors stage IDr. Cristina Ligia Cebotaru – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca


09:00 – 10:40 (VIENA HALL)Course for Oncology Nurses Coordinator Dr. Claudia Ordeanu Institute of Oncology „Ion Chiricuţă” Cluj-Napoca


11:00 – 12:40 (ATENA HALL)Treatment Session (III)Moderators: Prof. Dr. C. Chiricuţă, Assoc. Prof. Dr. A. C. Rancea

11:00 – 11:30Should be the immediate silicone breast implantation in breast cancer patients postponed after performing the external beam radiotherapy?Prof. Dr. C. Chiricuţă – Amethyst Radiotherapy Center, Otopeni

11:30 – 11:50Update on breast reconstruction techniques and indications - Surgeon point of view.Dr. A. Martin – Medestet Center Cluj-Napoca

11:50 – 12:10Radiotherapy and breast reconstruction timing and clinical outcomes - Radiation oncologist point of view.Dr. Daniela Martin – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

12:10 – 12:25Physicist point of viewPhys. D. Dordai – Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

12:2 – 12:40 The treatment planning using VMAT for immediate implant breast cancer surgeryPhys. R. Popa – Amethyst Radiotherapy Center, Otopeni, Romania

11:00 – 12:40 (VIENA HALL)Course for Oncology Nurses Coordinator Dr. Claudia Ordeanu Institute of Oncology „Ion Chiricuţă” Cluj-Napoca

12:40 – 13:00 (ATENA HALL) CONCLUSIONS – Congress closure

„Managementul îngrijirii pacienţilor cu afecţiuni neoplazice”

PROGRAM

SESIUNE ASISTENTE


SESIUNEA I – Sala Viena

Moderatori: Dr. C. Ordeanu si Dr. E. Ciuleanu

09:00 – 09:05 Deschiderea oficială

09:05 – 09:25Complicaţiile şi tratamentul radioterapiei pelvisului Dr. C. Ordeanu

09:25 – 09:45 Tratamentul mucozitei radiceDr. E. Ciuleanu

09:45 – 10:05 Tratamentul antialgic la bolnavii oncologici As. Univ. Dr. C. Burz

10:05 – 10:25 Urgenţe oncologice – Rolul asistentei medicale Dr. G. Hogea

10:25 – 11:00 – Pauza cafea

SESIUNEA II – Sala Viena

Moderatori: Prof. Dr. V. Nagy si Sef Lucr. Dr. C. Cainap

11:00 – 11:20 Tratamentul neutropenieiŞef Lucr. Dr. C. Cainap

11:20 – 11:40 Tratamentul anemiei – Indicaţii actuale Dr. C. Cebotaru

11:40 – 12:10Ghiduri practice – O schimbare în practica curentă As. Univ. Dr. Z. Fekete

12:10 – 12:40 Trialurile clinice – Ce trebuie să ştim despre ele Dr. A. Eniu

A B S T R A C T S

RESIDENT AFTERNOON

TREATMENT RESULTS IN NASOPHARYNGEAL CARCINOMA, THE EXPERIENCE OF THE ONCOLOGY INSTITUTE „PROF. DR. I. CHIRICUTA” CLUJCristian Turdeanu1, Elisabeta Ciuleanu1, Valentin Cernea1,2, Tudor Eliade Ciuleanu1,2, Danut Gheorghiu1, Octavian Chis1, Vasile Popita1, Nicolae Todor1, Liliana Resiga1, Victor Bogdan1

1) The Oncology Institute „Prof. Dr. I. Chiricuta” Cluj; 2) ”Iuliu Hatieganu” University of Medicine and Pharmacy Cluj

Aim of the study: to present a retrospective analysis of the cases with nasopharyngeal carcinoma, treated in the Oncology Institute „Prof. Dr. I. Chiricuta” Cluj, between 2006-2011. The end points were the analyses of prognostic factors for RR, OS and TTP.

Material and methods: 163 patients with nasopharyngeal carcinoma were treated. Median age was 44 years (range 15-78), 36,2 % were female, 63,8 % were male; 78,5 % of them had an undifferentiated cc., 14,1 % had a nonkeratinizing cc. and 7,3 % epidermoid cc.; 2,5 % of patients were stage I, 21,4% stage II, 41% stage III, 20,8 % stage IVA, 14 % stage IVB.

Results: 92,6 % of patients had induction chemotherapy (IC), (Epirubicin and Cisplatin – 90,7 % or Cisplatin and 5-Fluorouracil – 6,6%). All patients had RT; 86 % of them with Cisplatin as radiosensitizer.

Median follow up was 51 months. RR at the end of primary treatment was 93,86 % (89,57% CR; 4,29 % PR). RR was significantly influenced by: the stage (I, II, III vs IV) p<0.01; level of Hb (<10 gr vs >10gr) p<0.01; ESR value (<40 vs >40) p<0,01. There was a trend towards improved

RR function of age (<45 vs >45) not reaching significant statistical value p=0,06;

5 year-OS was 78% (IC:70 % - 85%). 5 year-OS was significantly influenced by: the stage ( I, II, III vs IV) p<0.01; Hb level (<10 gr vs >10gr) p<0.01; ESR value (<40 vs >40) p<0.01.There was a trend towards improved OS for undifferentiated and nonkeratinizing cc vs epidermoid cc.(p=0,06)

5 year-TTP was 71 %. It was significantly influenced by the stage ( I, II, III vs IV) p<0.01, and was a trend towards improved TTP for VSH value <40 vs >40, p<0.08.

Conclusions: Overall survival was significantly influenced by the stage, level of Hb, ESR value. There was a trend towards improved OS for undifferentiated cc. and nonkeratinizing cc vs epidermoid cc. TTP was significantly influenced by the stage.

COMPARISON OF THREE DIFFERENT TYPES OF TARGET VOLUME (PTV) DELINEATION ON POSTOPERATIVE CONFORMAL RADIOTHERAPY FOR PRIMARY BRAIN TUMORSRaluca Stăhiescu, Silviu Halaşag, Dana Cernea, Victor Bogdan

Institutul Oncologic “Ion Chiricuţă” Cluj Napoca

Background: there is a significant variability in PTV delineation in post-operative brain tumors due to unclear margins of residual tumor or residual cavity. We present the variability in target volume delineation using three different types of images.

Material and methods: this is a prospective study


of target volume delineation for 8 patients with different type of brain tumors: five with post-operative cavity and three with residual tumors. Planning CT without and with contrast enhancement was performed from vertex to C1-C2 vertebra with slices at 3mm for all patients. Target volumes and OAR have been delineated on planning CT without and with contrast enhancement in all patients. Fusion between planning CT with contrast and preoperative MRI was done in 5 patients. Isodose distributions, DVH, conformity index and volumetric differences were analyzed.

Results: comparing by DVH all target volumes where covered by 95%isodose, and the maximum tolerated dose for OAR was respected.

Volumetric differences between PTV where find: for patients with postoperative cavity, PTV on fusion planning was increased with >100cc (146-214,1cc) clinically significant, in 2 patients, and the contrast enhancement modified the PTV<100cc (3,2- 83,3cc) in three patients. For residual tumors the volumetric differences were<100 cc (6,6-81,3cc) for constrast and one100cc difference in fusion.

OAR irradiated volumes were better compared on DVH; volumetric differences very small: 5-10 cc. Conformity index (CI) was calculated: for patients with postoperative cavity CI was between 1,3-1,76 and for patients with residual tumors between1,45-1,56.

Conclusions: using planning CT with contrast and fusion with preoperative MRI could improve target volume delineation in patients with post-operative cavity which are not well defined or which are smaller then primary tumor or when the topography of the residual cavity is different.

NEO-ADJUVANT CHEMOTHERAPY IN LOCALLY ADVANCED CERVICAL CANCERNemes Adina1, Nagy Viorica2,3

1) Medical Oncology Department of “Ion Chiricuta” Institute of Oncolgy, Cluj; 2) Medical Oncology and Radiotherapy/ Brachytherapy Department of “Ion Chiricuta” Institute of Oncolgy, Cluj; 3) Iuliu Hatieganu” Medical University of Cluj, Romania

Objective: In this non randomized,feasibility study we assessed the response to neo-adjuvant chemotherapy in locally advanced cervical cancer.

Material and methods: 112 patients with cervical cancer stage IIB-III treated in the Oncology Institute Prof.Dr.I.Chiricuta Cluj-Napoca(OICN) between November 2010-September 2012 were included in this study.Patients received neo-adjuvant chemotherapy (NACT) 2 or 3 cycles, 2 regimens (Paclitaxel 175mg/m2 and Carboplatin AUC5(PC) or Topotecan 0.75mg/m2 and Cisplatin 50mg/m2(TC)) followed by concurrent radio-chemotherapy(RCT)

with Cisplatin (20mg/m25 days or 40mg/m2 weekly) or Carboplatin AUC2.Patients underwent external beam radiation therapy(EBRT) to a total dose(TD) of 46Gy;at 46Gy patients were evaluated for surgery and those with favorable parametrial response were optionally operated.Remaining patients underwent EBRT up to a TD of 60 Gy.EBRT was associated with brachytherapy (TD 10 or 20 Gy).Local response was assessed at the end of NACT,at the end of RCT and for operated patients by the pathological outcome.This study included 112 patients with locally advanced cervical cancer:st.IIB 31 patients(27,7%),st.IIIA 48 patients(42,9%) and st.IIIB 33 patients (29,5%) with a median age of 52 years(22-72 years old).85,7% of tumors were squamos cell carcinomas,8% adenocarcinomas and 6,3% were other histologies(adenosquamos carcinoma, clear cell carcinoma,small cell carcinoma).Median tumor size was 4 cm (1-7 cm).

Results: Out of 112 patients 84 patients(75%) performed NACT with PC and 28 patients (25%) performed NACT with TC.Objective response (OR=complete response(CR)+ partial response(PR)) to NACT was obtained in 59 patients(52,68%).PC was found to be superior to TC in terms of OR(57,14% vs. 39,29%),with a 17,85% difference,but without statistical significance(p=0.10).Also the number of NACT cycles(3 cycles vs 1-2 cycles) proved to be important for the response to NACT regarding CR(33,33% vs. 66,67% PC). With NACT we obtained a 10% improvement in therapeutic response(OR vs SD) in correlation with the stage of the disease(IIB 54,84% vs. 45,16%,IIIA 58,33% vs 41,67%, IIIB 42,42% vs. 57,58%)and with the histology(squamos cell carcinoma 54,17% vs. 45,83%,adenocarcinoma 55,56% vs. 44,44%,other histologies 28,57% vs. 71,43%).65 of the 112 pacients performed exclusive RCT with a CR in 14(21,54%) of patients and 47 patients underwent surgery with a CR in 19(40,43%) of patients,with a CR at the end of treatment of 29,46%.For the operated patients we observed a pathological CR(pCR) in 32 (68,9%) of 47 patients.The correlation between pCR and the administration of 3 cycles of NACT revealed a 78,95% CR for PC and a 55,56% CR for TC,showing again the superiority of PC.The hematologic toxicity observed in NACT was mild or moderate, most common toxicities were grade 1/2 with a higher rate of anemia and neutropenia.At a median follow-up of 17,4 months 98 patients(87,5%) presented CR,3 patients(2,68%) PR and 11 patients(9,82%) PD.

Conclusions: High response rates can be achieved with NACT in locally advanced cervical cancer,as the results we have obtained show,results that are consistent with recently published data.In terms of NACT regimen Paclitaxel and Carboplatin showed to be superior to Topotecan and Cisplatin and 3 cycles proved to be superior to 2 cycles with acceptable toxicity.Due to the small number of patients and short follow-up we were not able to assess overall survival.Randomized, larger number and long term evaluation trials are necessary in order to confirm these data.


CANCER INSTITUTE ”ION CHIRICUTA” EXPERIENCE IN NEOADJUVANT AND ADJUVANT TREATMENT IN BREAST CANCER PATIENTSAndreea Patrulescu1, Corina Campian1, Elisabeta Custura2, Daniela Grecea3

1) Medical Oncology Department of “Ion Chiricuta” Institute of Oncolgy, Cluj; 2) Radiotherapy Department of “Ion Chiricuta” Institute of Oncolgy, Cluj; 3) Medical Oncology and Radiotherapy Department of “Ion Chiricuta” Institute of Oncolgy, Cluj

Background:We evaluated the impact of neoadjuvant (NCT) and adjuvant (ACT) chemotherapy in breast cancer patients, treated in IOCN.

Methods :A retrospective study which includes 129 patients diagnosed with stage I-III breast cancer between 2005-2009, with a complete treatment and follow up in IOCN.

Results:From our cases, 39%(51) received ACT, the ones considered early breast cancer (EBC), and 60,47%(78) received NCT, considered locally advanced breast cancer(LABC).LABC: We compared the cases with a histological complete response / minimal residual disease (pT0N0+ p T1N1) vs. pT2-4N2-3 and found a DFS =80% vs.61% and OS=85% vs.63%(p=0,14 and p=0,25). DFS and OS was 69% and 76%, for the cases with positive hormonal receptors (HR) and 69% and 74% for negative HR. In regard to treatment, the cases which received antracyclines had a DFS of 56% and OS =87%, while the ones treated with sequential chemotherapy (antracyclines and taxane) had a DFS =48% and OS =85%. The patients with radical surgery (MRM) and pN0-1 with or without radiotherapy (RTE) had a DFS=81%vs.89% (p=0.76) and OS = 85%vs.83% (p=0.84).EBC: The patients with ACT and positive HR had a DFS=79 %, while for negative HR DFS=100%(p=0.14) and OS 91% VS 100% (p=0.35). For the patients who received ACT and MRM + RTE vs. MRM without RTE vs.Sectorectomy and limfadenectomy (SLA)+RTE, OS was 88% vs.100% vs.95% (p=0,43).

The patients with pT1N0-1 vs. pT2-4N2-3 had a DFS of 82% vs. 85%(p=0.90) and OS 100%vs.88% (p=0.13).

Conclusions:The add of taxanes to NCT had no benefit in DFS and OS (the patients had a reserved prognostic). The patients who received ACT, MRM and RTE vs. ACT, MRM without RTE vs. SLA and RTE showed no benefit in OS.

SECOND RADIOTHERAPY TREATMENT IN RECURRENT BRAIN TUMORSSilviu Halaşag, Dana Cernea, Raluca Stăhiescu, Victor Bogdan, Nicolae Todor

”Prof. Dr. Ion Chiricuţă” Oncology Institute, Cluj Napoca, Romania

Background: Radiotherapy for recurrent irradiated brain tumors is limited by toxicity effects. The purpose of this study is to determine whether second radiotherapy treatment is beneficial or not for patients with recurrent brain tumors.

Patients and methods: In a prospective study, 11 patients who recurred after primary brain tumors, first treated between 2005-2012, were analyzed for second radiotherapy treatment. Tumor histologic types are: glioblastoma multiforme (7), grade 2 astrocytoma (2), grade 3 oligodendroglioma (1) and grade 3 oligoastrocytoma (1). First radiotherapy (RT1) was performed with TD= 50-60Gy, 2Gy/ fraction, 8 patients, TD=30 GY, 3Gy/ fraction, one patient. DFS until the recurrence was 5.3-90.6 months. Second radiotherapy treatment (RT2) was associated with surgery and chemotherapy,8 patients, with surgery or chemotherapy 2 patients; RT alone in one patient. KI at RT2 was > 70 for 9 patients and < 70 for 2 patients. RT2 was delivered with: TD=10-44 Gy, 2 Gy/fraction,8 patients; TD=30-44 Gy, 2,66-3 Gy/ fraction, 3 patients. Site of recurrence, isodose distributions, PTV1 (RT1) and PTV2 (RT2), KI at the beginning and at the end of radiotherapy were compared.

Results: The site of recurrence was: central and marginal, 7 patients, at distance 4 patients. The same volume was second irradiated in 4 patients. PTV2 was greater than PTV1 only for 3 patients. KI was unchanged at the end of RT2 for 10 patients. Deterioration was observed in one patient. The median follow-up is 9,22 months (5,8-20,6 months). Six patients are alive, and 5 are dead.

Conclusion: There are few therapeutic options for patients with recurrent brain tumors. Regardless of histology, second radiotherapy could be one of these options alone or with other treatment methods for patients with good KI, surgery at time of recurrence and longer DFS from first treatment.

CAN AMPUTATION BE AVOIDED IN EARLY ANO-RECTAL ADENOCARCINOMAS?I. László1, Anamaria Sipos1, Diana Pop1, Margareta Bako1, G. Kacsó1,2

1) Institute of Oncology “Ion Chiricuţă” Cluj-Napoca; 2) University of Medicine and Pharmacy „Iuliu Haţieganu” Cluj-Napoca

Objectives: Evaluation of toxicity and effectiveness of HDR Ir192 brachytherapy in sphincter preservation as an alternative for patients with early ano-rectal adenocarcinomas (EARAK) .

Methods: Between 2005-2012, 12 patients with T1-2N0M0 EARAK received adjuvant brachytherapy after endoanal full thickness complete excision. An endorectal


cylinder was used for elderly patients with contraindication to anesthesia. Spinal anesthesia was used for the rest of them,with interstitial perineal needles. Doses ranged from 32Gy/5 fr to 42Gy/7 fr (BT only). Recurrences were evaluated clinically, by imaging and checked by biopsy.Toxicity was rated according to CTCAE 4.0 scale.

Results: Median follow-up was 3 years (12 to 68 months). Median age was 66 years, the sex-ratio was 3 in favor of women. Clinical and imaging staging was: 41.6% T1, 58.3% T2. Resection margins were negative in 7 patients and uncertain for the others. Specific survival at 3 years was 100% , relapse-free survival was 91.6%.Local control was 91.6 %, the single local recurrence being saved by rectal amputation (8.4%). Maximal acute and/or late toxicity was G1 50%, G2 8.3%. Anal incontinence was 58.3% G1 and 8.3% G2. There was no severe toxicity.

Conclusions: Interstitial brachytherapy can be considered a reasonable alternative to rectal amputation in early stage T1-2N0M0R0 ano-rectal adenocarcinomas, after complete endoanal excision.

BRACHYTHERAPY FOR HEAD AND NECK CANCERS- THE IOC EXPERIENCEAnamaria Sipos1, Laszlo Istvan1, Diana Patcas1, Octavian Chis1, Gabriel Kacsó1,2

1) Institutul Oncologic „Prof. Dr. I. Chiricuta” Cluj Napoca; 2) Universitatea de Medicina si Farmacie „Iuliu Hatieganu” Cluj Napoca

Aim: Evaluation of brachytherapy (BT) efficacy and toxicity in head and neck cancers (HNC).

Material and methods: From 2004 to 2013, 23 patients had BT for NHC at the Oncologic Institute Cluj, based on one of three indications, which defined 3 groups of patients: A) second localizations/local recurrence in previously irradiated areas; B) after conservative resection for positive/close margins (< 5 mm) or C) as boost after chemoradiation (RCT).

Results: With a median age of 52 years [36-76], 2:1 male/female ratio, squamous carcinomas all but one adenoid cystic, 5 (21.74%) were oropharynx and 18 (78.26%) oral cavity cancers. The in-house protocol was:

- Group A: 6 patients (all N0M0) - had initial surgical treatment (3 were pT1-T2) followed by BT (39Gy/13 fr/ bid), 1 patient (T3 base of the tongue), and 2 with local recurrence after initial treatment got exclusive BT 54-55Gy/10fr/bid.

- Group B: 10 patients (3 pT1, 6 pT2, and 1 pT3, all N0M0) had positive margins 2, and 7 with close margins. The TD was 39-42 Gy/13-14fr/bid.

- Group C: 7 patients (1 with initial surgery followed by

RCT and BT Boost). TD range was between 18-30 Gy/5-10fr/3-7days, with 3-4Gy/fr.

The local control was: 83.34%, 90%, 71.43 % for groups A, B and C (overall local control was 82,61%) whereas late toxicity was noted for 5 patients (radionecrosis); 4 were G1-G2 healing after conservative treatment but one had radical surgery (G3-4). At the last follow-up 13% of patients had G2 xerostomia and 8.7 % developed G2 fibrosis. Local failure occurred in 4 subjects, 1 patient after 9 years, all others within 1 year after BT.

Conclusion: BT has definitely a role in the management of HNC, being the best choice with curative intention in selected patents with local recurrence or a second HNC in previously irradiated areas. Technical precaution should be taken to minimize the risk of radionecrosis.

STAGE I TESTICULAR SEMINOMA: RESULTS OF SURVIVAL AND RISK FACTORS FOR RELAPSENicoleta Zenovia Antone, Cristina Ligia Cebotaru, Monica Groza, Nicolae Todor

Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca

Objective: evaluation of adjuvant treatment and risk factors for relapse for stage I testicular seminoma..

Material and methods: retrospective study evaluated 112 patients aged between 18 and 78 years (medium age-37,4 years) stage I testicular seminoma between January 1982-January 2007, treated at Ion Chiricuta Cancer Center, Cluj-Napoca. The medium follow-up period was 135,8 months (range minimum 3 month-maximum 233 months). Demographic, clinical and paraclinical parameters of patients were observed.

Chemotherapy regimen administered in adjuvant setting was 1 cycle Carboplatin AUC 7 or 2 cycles Carboplatin AUC 6 for 31 (27,68%) patients for stage I seminoma, 44 (39,29%) patients were treated with adjuvant radiotherapy and 37 (33,04) were managed by surveillance.

Results: Overall survival at 10 years was 92%(CI: 85%-96%).

Eighty seven seminoma patients (77,68%) have not presented relapse, metastatic relapse was observed at 5 patients (4,46%), pelvic or lumboaortic lymph nodes was present at 17 patients (15,18%), metastatic and adenopathy relapse at 2 patients (1,79%) and seric relapse at 1 patient(0,89%).

Risk factors evaluated for relapse were age at presentation (p=0,1), performance status(p<0,1), stage of disease at presentation(p<0,1) and presence of markers(p=0,1).

Chemotherapy toxicity was moderate, main toxicity for Carboplatin was thrombocytopenia (6,67%), anemia(3,7%), leucopenia (3,33%), and nausea and vomiting (3,33%).


Conclusion: Stage I seminoma tumor prognostic is excellent. The rate of curability for adjuvant treatment is high, the overall survival at 10 years with adjuvant chemotherapy

is 96%, followed by adjuvant radiotherapy 93% and overall survival for patients treated with orchiectomy followed by surveillance is 41%.

INCIDENCE OF THYROID CANCER IN CLUJ COUNTY, 1998-2009Ofelia Şuteu1,2, Daniela Coza2, Luciana Neamţiu2, Florian Nicula2

1) „Iuliu Haţieganu” UMPh Cluj-Napoca; 2) „Prof. Dr. Ion Chiricuţă” Cancer Institute Cluj-Napoca

Introduction. In 2009, thyroid cancer (TC) ranked 6th among women from Cluj County, accounting for about 5% of all newly diagnosed female cancers. The study aimed to analyse the changes in incidence of TC in Cluj County during a 12-year period.

Method. We identified TC cases registered from 1998 through 2009 in the North-Western Regional Cancer Registry of Cluj. Information on date of diagnosis, histological type and tumour size was recorded. Age standardised incidence rates using World Standard Population were determined. Standardised incidence rate ratios (RR) with their 95% confidence interval (CI) were computed.

Results. A total of 422 TC cases were registered from 1998 to 2009, more common among females, 358 (85%) than males, 64 (15%), with a 5.6:1 ratio. The overall age-adjusted incidence rate of TC has been increasing in Cluj County from 3.63/100000 in 1998 to 13.44/100000 in 2009 in females, RR=4.49 (CI 2.60-7.73, p<0.0001) and from 1.30/100000 to 1.83/100000 in males, RR=1.62 (CI 0.58-4.55, p=0.50). The greatest increase of the incidence occurred in women over 45 years, especially in the age groups 50-59, RR=19.54 (CI 2.64-144.6) and 60-69, RR=8.55 (CI 1.97-37,18) (p<0.0001). 94% of cases were confirmed histologically as primary tumour. Papillary carcinoma was the most common subtype, accounting for 76% (319/422) of cases. The incidence of papillary cancer increased progressively over the study period: RR=6.02 (CI 3.07-11.78, p<0.0001). Tumours less than 2 cm were found in 82% of the 130 cases

of papillary carcinoma, for which information about size was available (2006-2009).

Conclusion. The increased incidence of TC in Cluj County may be apparent, partly due to increased detection and also to progressive improvement of case reporting to Cancer Registry. A true increase of the incidence is suggested by the ascending incidence among females more than males and the rise almost exclusively of papillary tumours.

CANCER SURVEILLANCE IN NORTH-WESTERN REGION OF ROMANIA. RECENT TRENDS IN MAJOR CANCERS INCIDENCE AND MORTALITYDaniela Coza1, Florian Al. Nicula1, Ofelia Suteu1,2, Luciana Neamtiu1, Marton AnnaMaria1, Sirbu Mihaela1, Lovasz Lidia1

1) The Oncology Institute „Prof. Dr. Ion Chiricuta”; 2) University of Medicine and Pharmacy „Iuliu Hatieganu”

Introduction. The Oncology Institute “Prof. Ion Chiricuta”, from Cluj (IOCN), Romania, always had major fields of interest in cancer registration and prevention activities. Hospital-based Cancer Registry of IOCN, functional since 1955, constitutes the core for the Population-based Cancer Registry (starting with 2008) named North-Western Regional Cancer Registry (NWRCR). NWRCR carried out the developing of the on-growing database, the setup of the network, coordinated the cancer registration related activities, performed periodical training for the staff involved, evaluated performance, measured the quality and completeness of data.

Method and material. The NW RCR is planned and

EPIDEMIOLOGY SESSION


organized with respect to European Network of Cancer Registries rules and standards. Covered aria: 34,159 kmp (14,32% from Romania surface) and 2,714,118 people (12.7% from national population). The incidence data were analyzed for the main malignancies in the NW Region and for mortality, in counties that provide data concerning deaths (Cluj, Bistrita Nasaud, Maramures). The crude and standardized rates (through direct method) were calculated for incidence and mortality.

Results. In NW Region counties, in males, lung cancer ranks first, followed by prostate cancer, and colorectal cancer. In females, breast cancer ranks first, followed by cervical cancer, colon cancer, endometrial cancer and lung cancer. Cumulatively, in 2009, gynecological, breast and colorectal cancers have been present in 53% of the totality of new cancer cases in women. In concerns of mortality, women are most often victims of breast cancer, followed by gynecological and colorectal cancers, as opposed to men who are more likely to die from lung cancer followed by colorectal cancer.

Conclusions. NWRCR is meant to produce estimates of the cancer burden in population, incidence, mortality and survival data. Among the most important malignancies in our Region are those for which are available measures of primary and secondary prevention, making compulsory the introduction of efficient public health interventions.

THE ONCOLOGY INSTITUTE „ PROF. DR. ION CHIRICUTA” CANCER PREVENTION AND CONTROL DEPARTMENT REPORT ON CANCER CONTROL ACTIVITIESFlorian Al. Nicula1, Daniela Coza1, Luciana Neamţiu1, Ofelia Şuteu1,2, Patriciu Achimaş-Cadariu1,2, Alexandru Irimie1,2

1) The Oncology Institute „Prof. Dr. Ion Chiricuta” Cluj-Napoca; 2) University of Medicine and Pharmacy „Iuliu Hatieganu” Cluj-Napoca, Romania

Since 1929, as “Institute for the Study and Prevention of Cancer”, Oncology Institute from Cluj-Napoca (IOCN) developed epidemiological and public health activities.

From 1970’ies IOCN Epidemiology and Biostatistics Department had significant achievements:

- Cluj County Cancer Registry incidence data published in Cancer Incidence on Five Continents Volumes IV, V and VI;

- cervical and breast cancer opportunistic screening activities.

After 1990 new collaborative opportunities appeared:- first clinical databases connected to multicenter

databases (USA and Europe for Thyroid Cancer, FIGO databases, HPV prevalence studies databases - HERACLES / SCALES)

- from 1996 IOCN was directly involved in developing a National Strategy for Cancer Control, following a Meeting on Cancer Control evaluation for European Eastern Countries in Budapest, survey conducted by Max Parkin, former IARC President

Since the early 2000’s, under Prof. Dr. Alexandru Irimie Ministry of Health (MoH) Oncology Advisory Board presidency and IOCN leadership, a new Department of Cancer Prevention and Control (CPC) started to work with NW Regional Cancer Registry Unit, NW Regional Screening Management Unit and Cancer Control Planning Unit, with specific objectives:

- reorganization of population-based cancer registries in Romania; PHARE programme followed by a 8 regional cancer registries policy

- primary cancer prevention activities (all non-communicable diseases)

- cervical cancer screening programme from feasibility studies to pilot programme and national roll-out

- curricula and training in oncological subspecialties according to European guidelines (medical oncology, radiotherapy, oncological surgery and gynecology).

- elaboration and dissemination of multidisciplinary protocols of diagnosis treatment and follow-up

- collaboration with NGOs on palliative therapy, psycho-oncology, rehabilitation and reintegration of cancer patients.

In 2009 started the Joint Action EPAAC partnership for cancer control plans of the Member States of the European Union. IOCN - CPC worked in Steering Committee and all working groups (EUROCOURSE, EUROCHIP, EUROGIN , treatment, research and national cancer control plans).

In 2013 on MoH request IOCN and International Atomic Energy Agency (IAEA) developed an imPACT programme conducted by a IAEA-WHO team of experts, followed by a Report on cancer control in Romania.

IAEA launched this summer a new project in collaboration with seven institutes of oncology including IOCN-CPC, aiming to assess multidisciplinary cancer treatment figures.

IOCN-CPC drafted and submitted to MoH a National Cancer Control Plan for Romania, using French plan, with measures very similar to those required for Romania.

A new Joint Action will start in 2014, CANCON within IOCN-CPC will be leader of the Evaluation workpackage.

Future department plans are to continue with research and innovation, focusing on survival studies and treatment quality control studies, breast and colorectal pilot screening programmes, implementing regional cancer control plan and first cluster on oncology in NW region in collaboration with Harvard Business School.


SIGNIFICANCE OF CIRCULATING TUMOR CELLS IN CANCER THERAPY MANAGEMENTRares Buiga1, Tudor Ciuleanu1,2, Corneliu D. Olinici2, Ioana Neagoe1

1) The Oncology Institute „Prof. Dr. Ion Chiricuta” Cluj-Napoca; 2) University of Medicine and Pharmacy „Iuliu Hatieganu” Cluj-Napoca, Romania

Cancer is a major public health problem both in Western countries and in Romania. In general, cancer related death is caused by the occurrence of metastasis. The metastatic process begins with the migration of malignant cells from the primary tumor, followed by penetration into the circulation and their spread in the body. Circulating Tumor Cells (CTCs), released by primary or metastatic cancers, are viewed as the “leukemic phase” of the solid tumors and may represent one of the best tumoral biomarkers. Their presence in the bloodstream certifies the presence

of a metastatic tumor in the body, and their enumeration prooved to be prognostic marker for the clinical outcome of patients with various cancers like breast, colorectal and prostatic cancer. CTCs correlates well with overall survival and disease free survival. Monitoring CTCs after the removal of the tumor could be a valuable way to evaluate the efficacy of an adjuvant treatment. This method has the potential to assess the prognosis in an individual case and to show very quickly if a treatment is effective. Evaluation of CTCs, before and after treatment, may represent a means to predict relapse even in complete responders. Moreover, CTCs can be viewed as an equivalent of a „liquid biopsy”, guiding the selection of therapy based on their biomolecular analysis, so offering the perspective of a personalized therapy. Nevertheless, before it can be widely used in clinical setting, major improvements of the methods are needed, because identification of CTCs remains a difficult process. This presentation makes a brief review of the new techniques of CTC identification, highlighting some of the most promising clinical applications.

BIOLOGICAL IMAGING FOR RADIATION TREATMENT PLANNINGAnca-Ligia Grosu

Department of Radiation Oncology, University of Freiburg, Germany

The first rationale for using positron emission tomography (PET) in target volume delineation for radiation treatment planning is the higher sensitivity and specificity of PET for tumor tissue, in comparison to computed tomography (CT) and magnetic resonance imaging (MRI), in some tumor entities. This has been demonstrated in many studies, which compared the results of PET with the results of the radiological investigations and histology. The hypothesis tested in these studies, was that using PET in addition to CT and/or MRI, enables tumor tissue detection with a higher accuracy. The ideal PET tracer in this situation should be taken up homogenously from all the cells of the whole tumor and the intensity of the PET uptake should be directly proportional to the density of tumor cells.

The second rationale for integrating PET in the process of radiation treatment planning is the ability of PET to visualize biological pathways, which can be targeted by radiation therapy. The imaging of hypoxia, angiogenesis, proliferation, apoptosis etc. leads to the identification of different areas of an inhomogeneous tumor mass, areas of which can be individually targeted. For example, hypoxic areas can be treated with higher radiation doses than non-hypoxic areas.

The goal of this presentation is to discuss the use of PET for target delineation in the process of radiation treatment planning and monitoring.

DIAGNOSIS & NEW TECHNOLOGIES SESSION

PREDICTIVE ASSAYS IN CLINICAL ONCOLOGYIoana-Carmen Brie

Institute of Oncology „Prof. Dr. I. Chiricuta” Cluj-Napoca

Despite the great enthusiasm regarding the use of predictive and prognostic biomarkers, to date only few assays have met the standards allowing them to be used in guiding treatment decisions for improved outcomes.

The development of a prognostic or predictive assay that can guide treatment for cancer patients begins with the discovery of a molecular characteristic (“signature”) that correlates with a clinical outcome. The first step in developing such an assay is to define the intended clinical use for its result. For predictive and prognostic assays, the intended use consists in how the marker will assist the medical decision in a specific clinical situation. The next steps involve: optimization of the assay, including technical or analytical validation; clinical validation or evidence that the result of the assay correlates with the clinical outcome; and assessment of the clinical utility, meaning that the use of the assay results in a better outcome than standard methods or treatment.

Depending on the type of data obtained, there are several different types of assays: definitive quantitative assays, relative quantitative assays, quasi-quantitative assays and qualitative assays. An essential step in developing a predictive/prognostic assay is the analytical validation, involving assessments of its accuracy, precision, specificity and sensitivity. But, due to the lack of a gold standard assay, it is often very difficult to validate new biomarker assays.


The challenges for clinical assays development and acceptance by clinicians will be discussed, as well as the on-going projects regarding this topic in the Radiobiology and Tumor Biology Laboratory of the Institute of Oncology “Prof. Dr. I. Chiricuta” Cluj-Napoca.

MODERN ONCOLOGIC IMAGINGCristian Popiţa, Raluca Popiţa

”Prof. Dr.Ion Chiricuţă” Cancer Institute Cluj-Napoca

Explorările imagistice joacă un rol esenţial în managementul pacienţilor cu cancer. Ele au crescut în complexitate în ultimii ani şi continuă să se dezvolte.

Rolul radiologului în cadrul echipelor multidisciplinare de diagnostic şi tratament este esenţial şi este dependent, în mare parte, de abilitatea lui de comunicare cu ceilalţi membri ai echipei şi de informaţiile pe care reuşeşte să le transmită.

Alături de explorările morfologice, explorările funcţionale şi metabolice sunt deja prezente şi neîndoielnic vor oferi informaţii utile în diangnostic dar şi în monitorizarea post terapeutică.

Informaţiile sunt dependente în mare parte de cunoaşterea indicaţiilor şi limitelor acestor metode iar prezentarea noastră doreşte să sublinieze câteva din achiziţiile recente ale acestor metode imagistice, rolul şi locul lor în investigarea pacienţilor cu cancer.

“Wohle body“– CT, HR – CT, spectroscopia MRI, secvenţele MRI în difuzie şi perfuzie şi PET – CT vor fi succint discutate şi subliniate indicaţiile, limitele lor, raportul cost/beneficii şi riscurile biologice legate de iradiere, sau cele economice legate de costurile acestor proceduri.

DIGITAL BREAST TOMOSYNTHESIS IN BREAST CANCER DIAGNOSIS AND SCREENINGCarmen Lisencu

Oncology Institute “Ion Chiricuta”, Cluj-Napoca

Breast cancer remains one of the leading causes of cancer death in women. The use of full-field digital mammography (FFDM) has been shown to result in significant improvements in the radiologists‘ performance when interpreting examinations obtained particularly on younger women with dense breast tissue. However, conventional mammographic images are 2D radiographic views, and, as a result, the presence of overlapping dense fibroglandular breast tissue substantially reduces the conspicuity of some breast lesions. This thing limits the sensitivity of mammograph and it represents an important reason for missing breast cancers and for recalling a substantial fraction of women without breast cancer for a diagnostic workup. Full-field digital detectors with high resolution and large sensor size offer not only better contrast sensitivity, but also great opportunities to develop advanced digital imaging techniques that could improve conspicuity of breast lesions by enabling better tissue visualization through the provision of 3D non-overlapped tissue information.

Advances in digital imaging in general, and full-field digital mammography (FFDM) in particular, have led to the development of digital breast tomosynthesis imaging systems for 3D breast examinations. Digital breast tomosynthesis is of great interest for screening and diagnostic procedures because it enables 3D reconstruction. This ability allows cross-sectional visualization of breast tissue and it reduces the difficulty caused by the superposition or overlapping tissue in the interpretation of projected mammograms. In breast imaging, the potential benefits include the increasing of sensitivity of mammography in women with dense breast tissue ,as well as the possibility of reducing recall rates in screening mammography, improving the diagnosis of benign findings, and, consequently, reducing the number of biopsies with negative findings, also assessing therapeutic efficiency.

The purposes of this paper are to present a review of several studies about the advantages and limitations of digital tomosynthesis, and to show a personal experience with the use of this method in a short period of time at the Oncology Institute Cluj-Napoca .

TREATMENT SESSION I

CURRENT CONCEPTS AND CLINICAL EVIDENCE IN IMAGE GUIDED ADAPTIVE BRACHYTHERAPY OF CERVIX CANCER

Richard Pötter1,2

1) Department of Radiotherapy, Comprehensive Cancer Center; 2) General Hospital Vienna, Medical University of Vienna, Austria

Image guided adaptive brachytherapy (IGABT) for cervical cancer using MRI (CT, US) is an evolving method, increasingly replacing the traditional radiographic approach (2D). Image-assistance is provided for disease assessment, provisional treatment planning, applicator placement and reconstruction, as for contouring and definitive treatment planning. With IGABT changes of topography during treatment caused mainly by tumour regression (mean 75%) are identified and respected. Through IGABT significant improvement of dose volume parameters is achieved compared to 2D standard applications.

In small tumours the benefit is primarily obtained by a decrease of dose to nearby organs while in large and/or topographically unfavourable tumours the major benefit is through use of additional interstitial techniques and optimization. Dose response analysis shows that a dose ≥ 87 Gy for the target leads to tumor control of 90-95%. Respecting defined dose volume constraints for organs (e.g. 75 Gy for rectum) reduces adverse side effects by about 50%.

Mono-institutional data and emerging multi-institutional studies (STIC, EMBRACE, RetroEMBRACE) on IGABT show excellent local control (depending on dose level) with only few major late side effects. The Vienna series with mean 92 Gy in 156 patients reported a local control of 95% at 3

years with 6% Grade 3&4 late GU and GI toxicity (Pötter 2011). RetroEMBRACE data (11 centers) confirms these results: in 698 patients with mean 89 Gy, local control is 91 %, in stage IIIB 85%, at 3 years (Sturdza 2012).

Future developments will imply more frequent use of CT and especially US linked in various ways to MRI. Ultrasound (rectal and transabdominal) for interactive image guided application will facilitate individualized applications including additional interstitial brachytherapy.

With high local control rates through IGABT, the problem of metastatic disease will become more crucial (lymph node and systemic), in particular in high risk patient groups such as node positive and stage IIIB/IVA. This requires approaches for improved External Beam Radiotherapy in combination with IGABT and intensified chemotherapy. A new international trial (EMBRACE II) is under preparation investigating the role of adjuvant chemotherapy (CarboTax) within the clinical setting of IGABT.

IS SBRT THE FUTURE OF RT?

Ferran Guedea1,2

1) Catalan Institute of Oncology (ICO-DiR); 2) University of Barcelona (UB). Barcelona. Spain

In recent years, advances in information technology have generated an explosion of ever more powerful and sophisticated radiotherapy delivery systems. One of the most exciting developments is the emergence of stereotactic body radiotherapy (SBRT), which was originally developed for the curative treatment of peripheral, small-volume, medically-inoperable stage I non-small cell lung cancer (NSCLC).


SBRT utilizes real-time image guidance to achieve accurate anatomic target tracking while delivering very high doses of radiation. Although SBRT was initially limited to lung tumours, in recent years the number of indications has expanded to include other localizations (e.g, prostate, liver, adrenal glands) and larger tumour volumes.

In patients with inoperable lung cancer, early reports suggest that local control may be comparable to surgery. Our institution is currently carrying out a phase II trial at our institution for patients with stage I inoperable NSCLC treated by SBRT (3x 18 Gy). To date, we have treated 81 patients and early results in the first 38 patients are very encouraging: at 24 months, local control and overall survival are 96% and 79%, respectively. These are excellent results for this patient profile, and confirm the findings reported elsewhere. However, given that SBRT is still an emerging technology, more evidence is needed before it can be incorporated into standard practice. Fortunately, numerous clinical trials - including our own - are currently underway.

The most important concern surrounding this high-dose technique is the potential for excessive toxicity. The risk is not small, particular in lung cancer, given the continuous motion of the lung and the sensitive location in close proximity to vital organs.

Given the lack of long-term follow up and relatively small samples studied to date, SBRT should only be used in the context of clinical trials until more evidence of its safety and efficacy have been collected. Notwithstanding these caveats, SBRT appears poised to become one of the most important developments in the long history of the fight against cancer.

PRESENTING EUROPEAN GUIDELINES ON A RISK ASSESSMENT AND ANALYSIS OF ADVERSE EVENTS AND NEAR MISSES IN RADIOTHERAPY

J. Malicki, R. Bly, M Bulot, JL Godet, A Jahnen, H. Jarvinen, M. Krengli, R. Bly, M Bulot, JL Godet, A Jahnen, H. Jarvinen, J. Malicki, R. Bly, M Bulot, JL Godet, A Jahnen, H. Jarvinen, M Krengli, P Maingon, C Prieto Martin, K Przybylska, A Skrobala1, M Valero1

Greater Poland Cancer Center, Poznan, Poland

Aim: The main objective of the study was to conduct an EU-wide survey on implementation of the MED requirements aimed at the reduction of the probability and the magnitude of accidents in radiotherapy.

Description of the project: The Consortium of the ACCIRAD Project consists of six Partners: ESTRO, ASN with SECTOR as a subcontractor, FIB HCSC, TUDOR, and GPCC as the Consortium leader.

The workload within the Project is divided into 6 Work

Packages: WP1 – management and coordination, WP2 – questionnaire on MED implementation, WP3 – Risk analysis of accidental and unintended exposures, WP4 – Classification, reporting and registration of events, WP5 – European Guidelines, WP6 – European Workshop.

Results of the questionnaires: The General questionnaire was sent to 38 countries, from which 21 have replied. 10 more countries have provided some data, but have not finished the questionnaire. The second questionnaire covered more details of the available risk analysis systems, results of such analyses, as well as incident classification, reporting and registration systems.

The second questionnaire was completed by respective number of countries: detailed questionnaire -10, description of local proactive risk assessment/ and retrospective risk analysis -13, radiotherapy event report - 5, incident reporting systems- 20.

Support of the results : The Draft Guidelines (Patient safety in external beam radiotherapy – Guidelines on risk assessment and analysis of adverse events and near misses) were discussed during European Workshop on Risk Management in Radiotherapy in Poznań, Poland and were highly appreciated by all invited organizations.

Conclusions: Fifteen years after the introduction of EU Directive it became obvious that next step at an European level has to be made. The requirement for legal framework for risk analysis, classification of events, recording and reporting systems has not been addressed in some EU countries, and thus, the practical implementation of the systems in many countries is still incomplete.

SURVIVAL SCORES IN PALLIATIVE RADIOTHERAPYRades Dirk

University Hospital Schleswig-Holstein, Campus Lubeck, Germany

The patient’s survival prognosis should be considered to optimally tailor the treatment to a patient with metastatic disease. Estimating survival can be facilitated with a clear understanding of prognostic factors and survival scores. For patients with brain metastases, several survival scores exist. The first score including data of >1,000 patients was the RPA-classification, based on the data from three RTOG trials and published in 1997. RPA class 1 patients had KPS ≥70, controlled primary tumor, no extracranial metastases, and age <65 years. RPA class 2 patients had a KPS ≥70 and unfavorable prognostic factor(s), and RPA class 3 included all patients with a KPS <70. In 2008, the GPA including data from five RTOG trials was presented. It included age, KPS, number of brain metastases, and extracranial metastasis. Four prognostic groups were defined. Our own previous score published in 2008 aimed to reduce the risk


of a potential selection bias due to different treatments by including only patients receiving WBRT alone (N=1,085). Four prognostic groups were defined considering age, KPS, extracranial metastasis, and interval from first diagnosis of cancer until WBRT. To further reduce the risk of a bias due to heterogeneous treatments, we developed the WBRT-30, a validated score developed from data of 882 patients treated with 30 Gy in 10 fractions of WBRT. Predicting survival ≥6 months, the WBRT-30 was superior to other scores. For

patients irradiated for bone metastases, a score considering KPS, visceral metastases, and tumor type was published in 2005. Three prognostic groups were created. For patients irradiated for MSCC, a survival score designed from data of 1,852 patients has been validated and simplified. The simplified tool included three prognostic groups. The differences in survival of the prognostic groups were significant for all scores mentioned above. These scores contribute to an optimal personalization of treatment.

MICRORNA-21 STIMULATES GASTRIC CANCER GROWTH AND INVASION BY INHIBITING THE TUMOR SUPPRESSOR EFFECTS OF SERPINI-1, PDCD4 AND PTEN.Ciprian Tomuleasa1,2, Ling Li3, Sumitaka Yamanaka4, Fangmei An5, Florin Selaru6

1) „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania; 2) „Prof. Dr. Ion Chiricuta” Cancer Center, Cluj Napoca, Romania; 3) Peking University, Beijing, China; 4) Tokyo Medical University, Tokyo, Japan; 5) Shanghai Jiao Tong University, Shanghai, China; 6) The Johns Hopkins University School of Medicine, Bbaltimore, USA

Background and aims. Gastric cancer is the fourth most common lethal malignancy worldwide. Recent studies reveal that aberrant microRNAs play vital roles in oncogenesis via regulation of various gene expression or protein translation. MicroRNA-21 (miR-21) is abnormally expressed in many solid cancers such as gastric adenocarcinoma and regulates some targets involved in cancer initiation and progression. However, the mechanism is still poorly understood. In this study, we investigated the function of miR-21 in gastric cancer, as well as it’s potential targeting of the tumor suppressor genes Serpini-1, phosphatase and tensin homolog (PTEN) and programmed cell death protein 4 (PDCD4).

Methods. The first step was to use quantitative RT-PCR in order to to verify the overexpression of miR-21 in two different gastric cancer of cell lines. Western blotting confirmed the RT-PCR data in a set of rescue experiments that microRNA-21 mimic, inhibitor, negative and positive control. The protein levels of miR-21 targets Serpini-1, PTEN and PDCD4 was measured. Afterwards, we evaluated

it’s effect on tumor growth and invasion potential on two different gastric adenocarcinoma cell lines.

Results.RT-PCR results proved that miR-21 is overexpressed in gastric cancer cells when compared with normal gastric cells. Western blot results further suggest that PTEN and PDCD4 are regulated by miR-21, as miR-21 inhibitor increases the expression of PTEN and PDCD4 proteins and significantly reduces cell proliferation, migration and invasion. The control experiment proved that the miR-21 mimic significantly inhibits the expression of PTEN and PDCD4 proteins, leading to an increase in cell invasion and migration. Furthermore, and miR-21 inhibitor inhibits the apoptosis of gastric cancer cell lines.

Conclusions. MicroRNA-21 is overexpressed in gastric cancer and it’s aberrant expression may have important roles in gastric cancer growth and dissemination by modulating the expression of the tumor suppression genes PTEN and PDCD4, as well as the pathways involved in mediating cell growth, migration, invasion and apoptosis. Targeting of miR-21 may help us to develop novel therapeutics for gastric cancer, once it’s pathophysiology will have been completely described.

HUMAN BILE CONTAINS MICRORNA-LADEN EXOSOMES THAT CAN BE USED FOR CHOLANGIOCARCINOMA DIAGNOSISCiprian Tomuleasa1,2, Ling Li3, Sho Umegaki4, Anthony Kalloo5, Christos Giorgiades5, Mouen Khashab5, Staurt Amateau6, Timothy Pawlik5, Esteban Mezey5, Florin Selaru5

1) „Iuliu Hatieganu” University of Medicine and

POSTER SESSION I


Pharmacy, Cluj Napoca, Romania; 2) „Prof..Dr. Ion Chiricuta” Cancer Center, Cluj Napoca, Romania; 3) Peking University, Beijing, China; 4) Tohoku University, Sendai, Miyagi Japan; 5) The Johns Hopkins University School of Medicine, Baltimore, USA; 6) University of Colorado, Denver, Colorado, USA

Background and Aims: Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Consequently, significant efforts are needed to develop improved diagnostics. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither exosomes nor miRs within exosomes have been investigated in human bile. We aimed to comprehensively characterize human biliary exosomes, including their miR content.

Methods: Human bile specimens were obtained from patients under a Hopkins Institutional Review Board (IRB) approval. Specimens were processed for exosome isolation. The exosomes were analyzed with western blotting, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Multivariate Organization of Combinatorial Alterations (MOCA) was utilized to analyze the data and develop a miR-based CCA diagnostic panel.

Results: We have established the presence of exosomes in human bile. In addition, we have demonstrated that human biliary exosomes contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers and size distribution of human biliary exosomes. Finally, utilizing MOCA, we defined a novel biliary exosomal miR-based panel for CCA diagnosis which demonstrated a sensitivity of 60% and specificity of 93%.

Conclusion: This study reports the results of a comprehensive characterization of human biliary exosomes, including their miR content. In addition, these findings establish the importance of using exosomes, rather than whole bile, for developing miR-based disease markers in bile. The novel CCA panel developed herein represents a valuable addition to current diagnostic methods.

MICRORNA-126 MEDIATES THE INTERACTION OF CANCER ASSOCIATED FIBROBLASTS WITH MALIGNANT CELLS IN PRIMARY LIVER CANCERSCiprian Tomuleasa1,2, Masaharu Ishida3, Haoran Peng4, Sumitaka Yamanaka5, Victor Cristea1,6, Ioana Berindan-Neagoe1,2, Florin Selaru7

1) „Iuliu Hatieganu” University of Medicine and

Pharmacy, Cluj Napoca, Romania; 2) „Prof. Dr. Ion Chiricuta” Cancer Center, Cluj Napoca; 3) Tohoku University, Sendai, Japan; 4) Sun Yat Sen University of Medicine, Guangzhou, China; 5) Tokyo Medical University, Tokyo, Japan; 6) Octavian Fodor Regional Institute of Gastroenterology and Hepatology, Cluj Napoca, Romania; 7) The Johns Hopkins University School of Medicine, Baltimore, USA

The progression of cancer is a complex and clinically daunting process. Although recent findings revealed miRNAs as suppressors of cell-autonomous metastatic phenotypes, the roles of non-coding RNAs in non-cell-autonomous cancer progression processes remain unknown. Here we reveal that endogenous miR-126, an miRNA silenced in a variety of common human cancers, non-cell-autonomously regulates the forming of the surrounding desmoplastic stroma in both intrahepatic cholangiocarcinoma and hepatocellular carcinoma. It suppresses cancer cell growth and proliferation, metastatic cell invasion and metastasis by mediating the secretion of IGFBP2, IGFBP4, S100 A4, IL-2 and WISP1v, potential biomarkers of early cancer detection. Insulin-like growth factor binding protein 2 (IGFBP2) secreted by metastatic cells recruits fibroblasts by modulating IGF1-mediated activation of the IGF type-I receptor on endothelial cells; whereas the other cytokines stimulate cancer cell proliferation and invasion. Co-culture of fibroblasts cells with cancer cells non-cell-autonomously rescues their miR-126-induced metastatic defect, revealing a novel and important role for desmoplastic interactions in the initiation of malignancy. Through loss-of-function and epistasis experiments, we delineate an miRNA regulatory network‘s individual components as novel and cell-extrinsic regulators of fibroblastic involvement and metastatic colonization.

METFORMIN PLUS PIAF COMBINATION CHEMOTHERAPY FOR HEPATOCELLULAR CARCINOMA

Bobe Petrushev1, Ciprian Tomuleasa1,2, Olga Soritau2, Mihaela Aldea1, Gabriel Kacso1,2, Alexandru Irimie1,2, Ioana Berindan-Neagoe1,2

1) „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania; 2) „Prof. Dr. Ion Chiricuta” Cancer Center, Cluj Napoca, Romania

Background. Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin


exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy.

Methods. Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry.

Results. Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife-ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays.

Conclusion.Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer.

METFORMIN PLUS SORAFENIB – A NOVEL COMBINED THERAPY THAT HIGHLY IMPACTS GLIOBLASTOMA STEM-LIKE CELLS RESISTANT TO TEMOZOLOMIDEMihaela Aldea1, Ciprian Tomuleasa1,2, Bobe Petrushev1, Olga Soritau2, Gabriel Kacso1,2, Alexandru Irimie1,2, Ioan Stefan Florian1,3, Ioana Berindan-Neagoe1,2

1) „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj Napoca, Romania; 2) „Prof. Dr. Ion Chiricuta” Cancer Center, Cluj Napoca, Romania; 3) Neurosurgery Clinic, Cluj Napoca, Romania

Glioblastoma multiforme (GBM) is a highly infiltrative and deadly tumor of the central nervous system and spreads within the nervous tissue very fast, making neurosurgical resection almost impossible in most cases.This calls for a multidisciplinary approach that includes surgery and adjuvant radio-chemotherapy, followed by maintenance chemotherapy with temozolomide. However, the clinical efficacy of the current treatment is scant and the median survival after diagnosis of glioblastoma rarely exceeds 15

months. Previous studies in basic neuro-oncology have proven the existence of a small subpopulation of stem-like cells (GSC) that have the ability to undergo self-renewal and resistance to conventional chemo-radiotherapy thus initiating tumorigenesis and supporting ongoing tumor growth.

Encouraging results have emerged from recent data published on glioblastoma and point towards metformin, an oral-antidiabetic used for decades in the treatment of type 2 diabetes mellitus, as the most clinically relevant drug ever reported for targeting of glioma-initiating cells.The multikinase inhibitor sorafenib is undergoing phase I/II clinical trials in malignant gliomas. Sorafenib is approved by the FDA in the treatment of advanced renal cell carcinoma and unresectable hepatocellular carcinoma. The drug is regarded as a promising possibility in the treatment of malignant gliomas due to the inhibition of multiple oncologic kinases, such as raf, PDGFR, c-kit, VEGFR, which were proved to be overexpressed and confer a poor prognosis in a subset of glioblastoma tumors.

We found that sorafenib interacts with metformin in a greater than additive fashion to decrease cell proliferation, increase oxidative stress, inhibit efflux pump mechanisms and finaly to kill glioblastoma stem-like cells. Both metformin monotherapy and sorafenib monotherapy exert a selective cytotoxic effect on GSC, but insignificant effects upon differentiated glioblastoma cells, and metformin also does not affect human normal cells. Metformin plus sorafenib could be a potent therapy of glioblastoma stem cells, especially for those tumors that are resistant to temozolomide. Collectively, our study argue that GSC are highly sensitive to the combination between metformin and sorafenib and that this approach warrants further exploration in the clinic.

IMPLICATION OF ANTIANGIOGENIC INHIBITORS IN TRIPLE NEGATIVE BREAST CANCERCornelia Braicu1,2, Valentina Pilecki1,3, Roxana Cojocneanu Petric1, Braicu Ovidiu-Leonard1, Laura Pop1, Ioana Berindan-Neagoe1,2

1) Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2) Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta,” Cluj-Napoca, Romania; 3) Faculty of Pharmacy, „Iuliu Hatieganu” University of Medicine and Pharmacy

Triple negative breast cancer (TNBC) represents the most invasive subtype of breast cancer. As it shows no specific markers, it is laborious to find a targeted therapy.


It was proven that TNBC have a higher rate of angiogenesis, with a higher MVD (microvascular density) rate, raported to non-TNBC cases. After a initial feedback to chemotherapy, various patients with TNBC have recurrence to therapy. Novel therapies in TNBC targeting angiogenic pathways, especially in the case of combined therapy. The use of doxorubicine combined therapy with antiangiogenic short interfering RNA (siRNA) molecule in TNBC was leads to an increased therapeutic efficacy, fact demonstrated on in vitro TNBC cancer models. These findings reinforce testing a combination of TGF-β siRNA inhibitors with doxorubicine chemotherapy in TNBC patients. Additional investigations are required in order to find novel therapeutic targets in this type of malignancy.

PILOT STUDY FOR THE TARGETED SEQUENCING OF ACUTE MYELOID LEUKEMIA-ASSOCIATED GENES USING THE GS JUNIOR PLATFORM

Ciprian Tomuleasa1,2, Roxana Cojocneanu Petric1,3, Laura Pop1, Andrei Cucuianu2,4, Ioana Berindan-Neagoe1,5

1) Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2) Ion Chiricuta Cancer Center, Cluj Napoca, Romania; 3) Babes Bolyai University, Cluj Napoca; 4) Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca; 5) Department of Immunology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca

Introduction. Acute myeloid leukemia is a hematological disease diagnosed along with cytogenetic abnormalities at the hematopoietic stem cell level, involving genes related to cell growth and differentiation. The process involves what is known as the “two hit theory”, which defines the leukemic phenotype. The hits are represented by the maturation arrest and the aberrant proliferation, and the genes involved are NPM1, RAR, CBF, as well as FLT3, c-kit and MLL. Recent studies have shown that some other genes may take an active part in the development of the AML phenotype, such as CBL, KRAS and TET2. The purpose of the present pilot study was to observe the mutation status of these genes with the help of next generation sequencing technology in a number of three AML patients at the time of diagnosis.

Materials and methods. The aim of this pilot study was the Targeted Sequencing of AML-associated genes using the GS JUNIOR platform from Roche, and the genes studies were TET2, CBL and KRAS. For this, the peripheral blood collected from the patients at the time of diagnosis was separated using standard density gradient centrifugation, and DNA was extracted from the white blood cells. The

amplicons used for sequencing were obtained using the GS GType TET2/CBL/KRAS Primer Set which consists of oligonucleotide PCR primers for the amplification of exons 3-11 of TET2, exons 8-9 of CBL, and exons 2-3 of the KRAS genes. This process also included the attachment of molecular identification labels (MID) to each patient sample. The amplicon libraries that were obtained were quantified, quality checked and amplified by means of emulsion PCR, then the samples from all three patients were sequenced in a single run on the GS Junior machine.

Results and discussions. Upon completion of the sequencing run and data analysis, we have observed a total number of eight mutations, of which seven were in the TET2 gene, one in the CBL gene, and none in KRAS. Three of the mutations in TET2 were deletions at intron levels, the other four were substitutions, while the mutation observed in the CBL gene - homozygous in all three patients - was an exonic deletion which is most likely to cause a frame shift. Mutations of these three genes alter cellular biology at multiple levels and require not only the activation of receptor proximal signaling events but also an increase in cellular glucose metabolism. Pathways that are activated by CBL gain-of-function mutations can be efficiently targeted by small molecule drugs. Since the results of this pilot study may bring knowledge with the potential of influencing therapeutic approaches for AML, further research will be conducted in this direction.

THE INFLUENCE OF 5-FLUOROURACIL AND OXALIPLATIN ON THE INFLAMMATORY CYTOKINES AND RECEPTORS ON COLORECTAL CANCER CELL LINE COLO320Valentina Pileczki1,2, Claudia Gherman3, Cornelia Braicu1,3, Oana Virtic1,4, Roxana Cojocneanu Petric1, Ioana Berindan-Neagoe1,3

1) Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2) Faculty of Pharmacy, „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3) Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta,” Cluj-Napoca, Romania; 4) Faculty of General Medicine, „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

Introduction. Colorectal cancer is the third most common malignant disease in man and woman worldwide, with a high rate of mortality and with a continuously increasing number. Chemotherapy still is the best option after surgery for colorectal patients. Most frequently


used cytostatics ar 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) alone or in combined treatment. As most of the chemotherapeutic agents are known to interfere with nucleic acid metabolism and gene expression, we decided to determine the influence of those two agents on the cytokines involved in the development of colorectal cancer. Because the immune system plays an important role in the tumor microenvironment.

Materials and methods. The experiments were conducted on the Colo320 cell line, treated with 10μg/ml of 5-FU and L-OHP. After 24 hours from treatment the cells were harvested and total RNA extracted with the classical method of chloroform and isopropanol. PCR array analysis were carried out for 84 genes of inflammatory cytokines and receptors. For data interpretation and network generation the Ingenuity software was used.

Results. As a result of combination therapy of 5-FU and oxaliplatin we obtained the following statistically significant results, meaning data with a p value ≥ 0,05. 11 genes were found to be down-regulated and 5 up-regulated.

Conclusions. After the combined treatment all 11 up-regulated genes belong to cytokines and pro-inflammatory cytokine that support the synthesis and induce antigen expression on tumor cell surface, thus making it possible for the cells of the immune system to recognize and destroy tumor cells. Therefore the combined treatment may have prognostic or diagnostic value and an important role in the design of combined treatment with cytostatic.

CEREBRAL METASTASES-PREOPERATIVE DIAGNOSTIC, POSSIBLE OR NOT?Stanca Mihaela Ples1,3, Horia Ples1,2,3, Gabriela Catau3

1) Department of Neurosurgery, County Hospital Timisoara; 2) University of Medicine and Pharmacy „Victor Babes” Timisoara; 3) Diagnostic Imaging Center „Neuromed” Timisoara

New development in imaging technologies brings for neurosurgeons important preoperative and postoperative prospects for intracranial lesions and especially for cerebral metastatic disease evaluation. The new MRI techniques we currently use in Neurosurgical Clinic, County Hospital Timisoara are: DTI (diffusion tensor imaging), DWI(diffusion weighted imaging ), cerebral spectroscopy, SWI (susceptibility weighted imaging), cerebral perfusion (PWI) DTI (diffusion tensor imaging) - MRI technique- application is useful for localizing white mater tracts in relation with intracranial lesions, MRI SPECTROSCOPY can evaluate intra-lesional components (metabolites). Offers the opportunity for establishing differential diagnosis (ischemic, inflammatory, tumoral). In tumor pathology it is used to establish tumoral grading, and to differentiate the

metastatic from primary cerebral tumors. SWI (susceptibility weighted imaging) - a very new sequence in MRI which evaluates magnetic properties of blood, iron and other structures. Now it is used for diffuse axonal injuries, micro bleeds, angiogenes in tumors, venous angiomas ( slow flow vessels). Acquisitions are made with 1,5 T MRI, Avanto in Neuromed Diagnostic Image Center Timisoara. Conclusions using new imaging technologies we can, with 95% sensitivity and 91% sensibility of this methods, to establish the metabolic lesional components. Our study tries to make the difference in cerebral lesional evaluation of primary cerebral tumors from metastatic cerebral lesions.

Introduction: New development in imaging technologies brings for neurosurgeons important preoperative and postoperative prospects for intracranial lesions and especially for cerebral metastatic disease evaluation .The new MRI techniques we currently use in Neurosurgical Clinic, County Hospital Timisoara are: DTI (diffusion tensor imaging), DWI (diffusion weighted imaging), cerebral spectroscopy, SWI (susceptibility weighted imaging), cerebral perfusion (PWI).

Aim: Our study tries to make the difference in cerebral lesional evaluation of primary cerebral tumors from metastatic cerebral lesions.

Case report: Our study is made for 30 patients with secondary cerebral tumors.

Material and methods: Acquisition is made with 1,5 T MRI in Neuromed Diagnostic Image Center Timisoara. Used MRI techniques are: DTI (diffusion tensor imaging) - MRI technique-application is useful for localizing white mater tracts in relation with intracranial lesions, MRI SPECTROSCOPY can evaluate intra-lesional components (metabolites). Offers the opportunity for establishing differential diagnosis (ischemic inflammatory, tumoral). In tumor pathology it is used to establish tumoral grading, and to differentiate the metastatic from primary cerebral tumors. SWI (susceptibility weighted imaging) - a very new sequence in MRI which evaluates magnetic properties of blood, iron and other structures. Now it is used for diffuse axonal injuries, micro bleeds, angiogenesis in tumors, venous angiomas ( slow flow vessels).

Results: Using new imaging technologies we can, with 95% sensitivity and 81% specificity of this methods, to establish the metabolic lesional components.

Conclusion: Using new imaging technologies we can, with 95% sensitivity and 81% specificity of this methods, to establish the metabolic lesional components. Our study tries to make the difference in cerebral lesional evaluation of primary cerebral tumors from metastatic cerebral lesions.

CONTROVERSIES IN PATHOLOGICAL BONE FRACTURE OF THE SPINEStanca Mihaela Ples1,3, Horia Ples1,2,3, Gabriela Catau3



New imaging technologies offer for neurosurgeons important preoperative and postoperative data for spinal fractures. It is possible now to make the differential diagnosis for pathological bone fracture, to distinguish the tumoral from osteoporotic fractures. The new MRI techniques we currently use in Neurosurgical Clinic, County Hospital Timisoara are: diffusion weighted image (DWI) and spectroscopy (H-MRS) MRI SPECTROSCOPY can evaluate intra-lesional components ( metabolites ). Offers the opportunity for establishing differential diagnosis (inflammatory, tumoral, osteoporosis) DIFFUSION WEIGHTED IMAGING (DWI)-is using the water diffusivity properties; the ADC coefficient is very different in osteoporotic comparing with tumoral fractures, helping in differential diagnosis. Acquisitions are made with 1,5 T MRI, SIEMENS, Avanto. We have examined 15 pacients with pathological bone fracture of spine: 10 osteoporotic and 5 neoplasic fractures . 13 pacient needed surgery and we have anatomo-pathological examination for this patients. Conclusions: Using new imaging technologies we can, with 86% sensitivity of this methods, to establish the metabolic lesional components. Our study make the differential diagnosis in pathological bone fractures using diffusion and MR spectroscopy.

Introduction: New imaging technologies offer for neurosurgeons important preoperative and postoperative data for spinal fractures. It is possible now to make the differential diagnosis for pathological bone fracture, to distinguish the tumoral from osteoporotic fractures. The new MRI techniques we currently use in Neurosurgical Clinic, County Hospital Timisoara are: diffusion weighted image (DWI) and spectroscopy (H-MRS)

Aim: To evaluate if it is possible now to make the differential diagnosis for pathological bone fracture, to distinguish the tumoral from osteoporotic fractures.

Case report: We have examined 15 patients with pathological bone fracture of spine : 10 osteoporotic and 5 neoplasic fractures . 13 patient needed surgery and we have anatomo-pathological examination for this patients.

Material and methods: MRI SPECTROSCOPY can evaluate intra-lesional components (metabolites). Offers the opportunity for establishing differential diagnosis (inflammatory, tumoral, osteoporosis) DIFFUSION WEIGHTED IMAGING (DWI)- is using the water diffusivity properties; the ADC coefficient is very different as value in osteoporotic comparing with tumoral fractures, helping in differential diagnosis.

Results: Using new imaging technologies we can, with

86% sensitivity of this methods, to establish the metabolic lesional components of bone fractures of spine.

Conclusion: Our study succeed to make the differential diagnosis in pathological bone fractures using diffusion (DWI) and MR spectroscopy MR techniques.

SUPERIOR VENA CAVA SYNDROME IN PATIENTS WITH SMALL-CELL LUNG CANCERTeodora Alexa1,2, Simona Volovat1,2, Ancuta Varlan1, Carmen Bosteanu1, Lucian Miron1,2

1) Regional Institute of Oncology Iasi; 2) University of Medicine and Pharmacy Gr. T. Popa Iasi

Introducere. Sindromul de venă cavă superioară (SVCS) apare la diagnostic sau în evoluţie la pacientii cu cancer bronho-pulmonar microcelular (CBPM) în 10% din cazuri, prin invazie directă, prin compresiune tumorală sau prin adenopatii metastatice mediastinale.

Obiectiv. Evaluarea diferenţelor dintre pacienţii cu CBPM şi SVCS faţa de cei cu CBPM care nu au prezentat SVCS in evoluţie.

Material si metodă. Studiu retrospectiv a inclus pacienţi diagnosticati cu CBPM care au fost împărţiţi în două grupuri - grup A = prezenţa SVCS, grup B = absenţa SVCS. A fost efectuata analiza statistică pentru a identifica existenţa unei corelaţii între prezenţa acestui sindrom şi datele clinice, oncologice şi terapeutice colectate în baza de date. Testul Fischer şi testul Student t au fost utilizate; semnificaţia statistică a fost definită ca p<0.05.

Rezultate. Analiza nu a surprins diferenţe statistic semnificative în ceea ce priveşte vârsta, sexul, statusul tabagic sau stadiul neoplaziei la pacienţii din grupul A comparativ cu cei din grupul B. Toţi pacienţii incluşi în studiu au beneficiat de tratamentul standard al CBPM stadiul localizat (Cisplatin-Etoposid).O diferenţa semnificativă a fost înregistrată în ceea ce priveşte statusul ECOG, cu o valoare mediană de 2 în grupul A versus 1 în grupul B (p<0,05).

Modificările hematologice cele mai frecvente pentru ambele grupuri au fost anemia, leucopenia şi trombocitoza. O diferenţă statistic semnificativă a fost înregistrată în ceea ce priveşte gradul anemiei în cele două grupuri, cu o mediană de 2 în grupul A vs o mediană de 1 în grupul B (p<0.05); similar, grupul A a prezentat leucopenii mai severe comparativ cu grupul B (p<0.05).

Concluzii. Pacienţii cu CBP cu celule mici şi SVCS prezintă o probabilitate crescută de a dezvolta anemie şi leucopenie grad III comparativ cu pacienţii cu CBPM care nu evoluează cu SVCS, aspect care influenţează prognosticul, tratamentul (activ şi suportiv) şi evoluţia acestora.


RAPIDARC TECHNIQUE IN CRANIO-SPINAL IRRADIATIONA. Chis1,2, V. Mandea1, C. Taflan1

1) Centrul de Diagnostic si Tratament Oncologic Brasov; 2) Institutul Oncologic „Prof. I. Chiricuta” Cluj-Napoca

Introduction. Classical 2D and 3D techniques in cranio-spinal irradiation carry the problem of overdosing or underdosing at the junction between adjacent fields. At the same time doses received by organs at risk can be significant and are difficult to control because of the limited spacial distribution of the radiation fields used. These inconveniences are virtually eliminated by using the RapidArc technique. To obtain a homogeneous dose distribution throughout the target volume ( whole brain and entire medullary canal) we used a 3 izocentre and 6 arc tehnique.

Materials and methods. Patients were scanned with a GE Optima CT580 16 slice CT, with 2.5 mm distance between sections. Treatment planning was performed Eclipse 10 planning system, from Varian .Treatment plan verification was done with the a device specially used for VMAT plans, Arc Check manufactured by Sun Nuclear. A second check of dose-volume distribution was performed with 3DVH software from Sun Nuclear. DVHs were re-

calculated and verified with SNC 3DVH software using the original plan data and the delivered 3D dose distribution.

Patient immobilization was obtained using thermoplastic head mask and set-up accuracy was verified with OBI device (Kv) of a Varian Trilogy iX linac.

Results. This RapidArc treatment technique was used for the treatment of two patients with the diagnosis of medulloblastoma. In both cases PTV coverage was good (97% v 95% PTV dose) according to DVH and gamma-map analyses showed that 95% percent of the measured points were within the tolerance level. Gamma-map analysis was carried out by comparing the exported and measured data at 3 mm 3% tolerance level. The dose distributions was homogenius both in sagittal direction and transversal plans. Re-calculated DVHs differ from planned ones at a clinically irrelevant stage. Organs at risk doses were below those of the international protocols.

Conclusions. RapidArc compared to 3D conformal techniques offers a more conformal and homogeneous dose distribution in the target volumes and allows more organ at risk sparing. This comes at the cost of more time spent with treatment planning and verifications.

From the point of view of achieving treatment plan and especially the time required for treatment, RA technique is time consuming and energy.

FOLLOWUP IN OPERATED AND NON-OPERATED LOW GRADE GLIOMASStanca Mihaela Ples1,3, Horia Ples1,2,3, Gabriela Catau3


The follow -up in low grade gliomas can be accomplished in very good condition establishing protocols for each category of cases: operated and non -operated patients. In our clinic we have a 5 years followed -up 150 low grade gliomas: 85 operated , 65 non -operated. The protocol in this moment is: in first year, every 3 months conventional cerebral MR, in 2-nd and 3-d year every 6 month conventional MR, after that every year conventional cerebral MR. In every year we have a imaging neurodiagnose MRI made with spectroscopy, diffusion , perfusion and swi. Those protocols brings better results in this low grade gliomas follow-up. We can appreciate that by following this protocol. We can see the moment when this gliomas turn into high grade, and we appreciate the moment of recurrence in post surgical cases.

Introduction: The follow -up in low grade gliomas can be accomplished in very good condition establishing protocols for each category of cases: operated and non -operated patients.

Aim: The aim of our study was to share our experience in this difficult follow -up of low grade gliomas.

Case report: In our clinic we have in 5 years followed -up 150 low grade gliomas: 85 operated , 65 non -operated. The protocol in this moment is: in first year, every 3 months conventional cerebral MR, in 2-nd and 3-rd year every 6 month conventional MR, after that every year conventional cerebral MR.

POSTER SESSION II

Material and methods: In every year we have a neurodiagnostic imaging MRI made with spectroscopy , diffusion , perfusion and swi.

Results: Our results were good, better than before this period of non protocoled follow up in low grade gliomas.

Conclusion: We can appreciate that following this protocol we can see the moment when this gliomas turn in high grade, and to appreciate the moment of recurrence in post surgical cases.

PORT-A-CATH CHEMOTHERAPY ADMINISTRATION SYSTEM AT MEDISPROF ONCOLOGY DAY CLINICMariana Avram, Sorin Bochis, Anca David, Adrian Udrea

Medisprof Oncology Clinic, Cluj-Napoca

Port a cath systems are used for chemotherapy treatments, but they can also be used in the administration of antibiotics, blood transfusions, parenteral nutrition, administration of contrast material for MRI / CT and for medical test harvesting.

Benefits of port a cath systems are obvious: reduce the discomfort and pain associated with intravenous frequencies, they are discrete and aesthetic, they are mounted once and they can be used for many years, depending the material. They reduce the toxic effect of the treatment, the risk of infection and decrease the risk of venous thrombosis.

Given the use of port a cath systems for more than 20 years in developed countries for chemotherapy administration, we conducted a feasibility study among Medisprof clinic‘s patients in the introduction of routine port a cath systems. The multiple-choice questionnaire was used


in 62 patients (40.30% male, 57.70% female) in the period May-August 2013. Patients were aged between 22 and 83 years. Schemes most commonly used were: Epirubicin + Cyclophosphamide, Paclitaxel + Carboplatin, Etoposide + Carboplatin, Oxaliplatin + Irinotecan, Etoposide.

Results showed that approximately one third of our patients would and accepted port a cath system, 17,41 % refused due to financial reasons, 16,38% had a personal rejection of the idea and 9,21% did not accepted because of short chemotherapy.

In conclusion, for a cost that stands at 600 Ron for a port a cath system, one third of the patients agreed to install this device that has many advantages for the patient, but also for the medical staff.

PRIMARY HEPATOMA VERSUS LIVER METASTASES IN LIVER CIRRHOSISMintoiu Corina-Georgiana1, Tohanean-Dobre Mihaela1, Constantin Teodor Ionut1, Ditoiu Alecse Valerian1,2

1) Institutul Clinic Fundeni Bucuresti; 2) UMF Carol Davila, Bucuresti, Romania

Noticing the increased incidence of cancer in patients with cirrhosis, we intend to study this phenomenon.

Of the 516 patients diagnosed with liver cirrhosis hospitalized between 01.01.2012 – 30.06.2013, the study included 113 patients also diagnosed with a hepatic or extrahepatic neoplasm, with a prevalence of 21,88%.

Patient ages ranged between 20 and 80 years old, with the average age being 62,9 years, 44,25% of which were women.

As far as the etiology of cirrhosis is concerned, 48,67% of cases were viral, hepatitis C occurring in 27,43% of them, cryptogenic cirrhosis represented 43,36% and alcoholic cirrhosis 7,96% cases. The etiology of cirrhosis in patients with primary hepatoma was viral in 60% of cases, while in patients with metastasis, liver cirrhosis was mostly cryptogenic - 66,7% of cases.

The hepatic cancer is represented by 84,21% cases of primary hepatoma, respectively 15,79% metastases; 45,45% of them had the primary site in the digestive tube.

The cases of primary hepatoma are roughly equal in both genders( 51,25% males vs. 48,75% females) with an average age of the group of 63,07 years, while the liver mestastases are mainly meet at male gender -73,33%, the average age being 65,7 years.

From the point of view of Child‘s Classification, 50,44% of patients were Child B. Primary hepatoma occurred in 15% of Child C cases, while 6.66% already had metastatic disease.

In conclusion the prevalence of cancer in patients with cirrhosis is higher than general population; the liver cancer at

patients with cirrhosis is more frequent in Child s B class, the primary hepatoma is more frequent at cirrhotic pacients than metastases, gender distribution being roughly equal, while liver metastases being more frequently met in male gender in spite of the absence of male cancers( testis, prostate).

WHOLE BODY MAGNETIC RESONANCE INVESTIGATIONMariana Marusteri, Gabriela Catau

Diagnostic Imaging Center ”Neuromed” Timisoara

Aim of study: The study purpose consists in presenting this examination method, the recommendations, advantages and limits of usage, with examples from the clinic cases.

Material and method: One hundred case were examined at Neuromed during 2010-2013. The MRI device used was Siemens Magnetom Avanto 1,5T ,T Class, (76x32) RF channels with Tim technology. 45mT/m gradients, Tim CT Oncology software.

Results: 60% of the patients that underwent this type of investigation required it as a screening test, nu clinical signs were present at examination, but they wanted an investigation that would state they are healthy from an „imagistic” point of view.

40% of these cases presented various symptoms and underwent this investigation for diagnosis purposes.

Advantages of Whole Body MRI: It allows the diagnosis of disease without limiting to a specific anatomic region. It allows examining the entire body, without repositioning the patient or of the antenna, due to the Tim CT Oncology, Siemens technology.

Recommendations of WB-MRI: The method election recommendation is for oncologic patients for the diagnosis of the metastatic disease - Tim CT Oncology.

Examination limits: Differentiation of reactive lymph-nodules from the malignant ones remains a problem in certain cases. The differentiation of post-surgery scars of a residual tumor or a tumor relapse may be difficult in certain situations. Organ-specific problems may occur in detecting metastases or a synchro-metastasis.

Conclusions: It is a non-irradiating method that allows the examination of the entire body.

The election indication is represented by the metastatic disease diagnosis or of other pathologies affecting multiple anatomic regions.

It does not exclude other examination methods; these may sometimes be necessary as complementary methods: e.g. CT in lung lesions or other cases of bone lesions.

If a lesion is identified during screening for metastases and the diagnosis is unclear, a MRI for the respective segment is performed.


THE INCIDENCE OF CANCER IN LIVER CIRRHOSISCorina Georgiana Mintoiu1, Mihaela Tohanean Dobre1, Teodor Ionut Constantin1, Alecse Valerian Ditoiu1,2

1) Institutul Clinic Fundeni Bucuresti; 2) UMF Carol Davila Bucuresti

Noticing in literature the increased incidence of cancer in patients with liver cirrhosis, we intend to study this phenomenon by comparing it to the study „ Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark”*.

The prevalence of cancer in cirrhosis is higher in our study -21,88% versus 12,47%.

Gender distribution is roughly equal in both studies, the average age is higher in our group -62,9 years vs. 55,05 years.

The etiology of cirrhosis is completely different, in the Danish study the etiology is alcoholic -60%, while in our study the etiology is viral -48,67%, the C virus alone represents 27,43% of the viral cases. In Denmark, viral infections are very low in general population, they didn‘t t included the viral etiology in the study.

The hepatoma is the tumor with a majority proportion in both studies, but with a big difference; in our study the hepatoma represents 70,79%, while in the Danish study only 16,93%, this important difference between this two being the etiology.

Another observation is the presence of cancer in the digestive tract, both studies presents roughly equal – 15,04% in our study vs. 16,61%, in this case the etiology of liver cirrhosis did not affect the incidence of cancer.

In conclusion, the liver cirrhosis is a risk factor for the appearance of cancer, extrahepatic also. Our country has a higher incidence of viral infections, causing cirrhosis and liver cancer, while the Danish population is more exposed to risks caused by alcohol consumption and occurrence of cancer and in other location than liver. The difference between the average age can be explained by the quicker time that alcohol affects the liver.

*Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, Trichopoulos D, Vilstrup H, Olsen J.

EFFECTIVENESS OF CHEMOTHERAPY IN ELDERLY PATIENTS WITH METASTATIC LUNG CANCER IN CLINICAL PRACTICEPostolache Eva1, Cocea Corina1, Murgulet Elena1, Gafton Bogdan1,2, Miron Lucian1,2

1) Instittul Regional de Oncologie Iasi; 2) Universitatea de Medicina si Farmacie Grigore T Popa Iasi

Îmbătrânirea este un proces multifactorial, heterogen. Prin urmare, modificările anatomice, fiziologice şi funcţionale legate de procesul de îmbătrânire sunt foarte variabile de la un ţesut la altul, de la un organ la altul, de la un individ la altul.

Vârsta “per se” reprezinta un factor de risc important pentru boala neoplazica, dar nu o contraindicaţie pentru chimioterapiei. Un bilanţ geriatric corespunzator este recomandat pentru a evalua oportunitatea chimioterapie.

Localizarile cele mai frecvente ale bolii neoplazice în rândul populaţiei geriatrice sunt reprezentate de prostată, plămân, sân, vezică urinară, stomac şi colon, proporţia variind de la 51% pentru plămân, până la 77% pentru prostată.

Am urmărit răspunsul terapeutic şi impactul tratamentului oncologic asupra calitaţii vieţii pacientului S.D., în vârstă de 75 ani, hipertensiv cu un status de performanţă bun (ECOG=1), diagnosticat imagistic şi biopsic cu adenocarcinom bronhopulmonar stadiul IV (plămân, os), pentru care s-a iniţiat chimioterapie paliativă cu Carboplatin şi Paclitaxel, tratament cu bisfosfonaţi, ulterior adăugându-se şi terapie ţintită cu Bevacizumab. Pacientul a tolerat bine tratamentul, prezentând toxicitate neurologica grad I, HTA gr.3, un episod de epistaxis remis spontan.

Rezultate : Clinic - ameliorarea calităţii vieţii. Evaluare imagistica după 6 cicluri de tratament evidenţiaza aspect de răspuns parţial la nivel pulmonar.

Concluzii: Pacienţii vârstnici “fit” beneficiaza de pe urma dubletului de chimioterapie pe baza de săruri de platină. Bevacizumabul în asociere cu Carboplatin+Paclitaxel împunătăţeşte supravieţuirea la pacienţii cu neoplasm bronho-pulmonar non-microcelular.

Cuvinte cheie : vârstnicul, adenocarcinomul bronho-pulmonar, chimioterapie

MAINTENANCE THERAPY RESULTS IN STAGE IV LUNG ADENOCARCINOMA

Murgulet Elena1, Postolache Eva Maria1, Pruteanu Cristina1, Clement Dana1, Miron Lucian1,2

1) Institutul Regional de Oncologie Iasi; 2) Universitatea de Medicina si Farmacie Grigore T Popa IasI

Neoplasmul brohopulmonar are o incidenţă în Europa de 52/100.000 persoane pe an şi este cel mai frecvent tip de cancer întâlnit la bărbaţi.

Pacient M.D. in varsta de 39 ani, nefumator, relateaza debutul insidios al bolii in februarie 2012, prin durere la nivelul hemitoracelui stang, hemoptizii, astenie si scadere ponderala.

In martie 2012 a efectuat un ex CT craniu- torace-abdomen ce a evidentiat: aspect sugestiv pentru neoplasm bronhopulmonar lob inferior stang, cu noduli pulmonari


ipsilaterali (T4), multiple adenopatii hilare stangi si mediastinale bilateral (N3), multiple formatiuni cu caracter de leziuni secundare osoase, pulmonare si cerebrale(M1b).

S-a intervenit chirurgical si s-a practicat toracotomie antero-laterala stanga cu biopsie pulmonara stanga, cu BAP: adenocarcinom pulmonar mixt (acinar si papilar), cu invazie pleurala, vasculara si perineurala.

In martie 2012 s-a initiat chimioterapia paliativa cu Cisplatin si Gemcitabina, tratament cu bisfosfonati, iar in aprilie a efectuat radioterapie cerebrala, fara toxicitati acute.

In iulie 2012 s-a initiat chimioterapia de mentenanta cu Pemetrexed. Evaluarea imagistica dupa un an de tratament evidentiaza aspect stationar la nivel pulmonar si osos si raspuns partial la nivelul metastazelor cerebrale.

Concluzii: Pacientii tineri cu un status de performanta bun, fara comorbiditati associate, beneficiaza mai mult de pe urma chimioterapiei si terapiei de mentenanta chiar si in std IV de boala. In cazul nostru s-a obtinut in urma terapiei de mentenanta o crestere a supravietuirii de la o medie de 8 luni la 16 luni, cu o mentinere a aspecutlui de boala stationara.

CHANGES IN THE PLASMA LEVELS OF TGF-BETA-2 AND GDF-15 IN RESPONSE TO RADIOTHERAPY IN BREAST CANCER PATIENTS

Boglárka Schilling-Tóth1, Nikolett Sándor1, Zoltán Varga2, Zsuzsanna Kahán2, Géza Sáfrány1, Hargita Hegyesi1

1) Frédéric Joliot-Curie National Research Institute for Radiationbiology and Radiationhygiene, Anna str. 5, H-1221 Budapest, Hungary; 2) University of Szeged Department of Oncotherapy,Korányifasor 12. H-6720 Szeged, Hungary

Background: Radiotherapy plays an important role in the management of breast cancer and can reduce the local and

regional recurrence, thereby improving outcomes. Adverse events following irradiation (IR) for breast cancer include pain and hyperpigmentation, skin ulcerations, lung and soft tissue fibrosis or late cardiovascular damage. Number of studies reported that the overall frequency of adverse events after radiotherapy were 1-2% in women with breast cancer. Several reports suggested that alterations in the serum levels of TGFmight be predictive for the development of late sequels in radiotherapy patients. Unfortunately, other reports were unable to confirm these data. In the present paperalterations in the plasma levels of GDF15 and TGFβ2 were evaluated for their potential predictive value in the development of radiation-induced lung fibrosis.

Materials and methods:Peripheral blood plasma was isolated from 21 primary breast cancer patients before and3, 6 and 21 weeks after radiation therapy (RT). The plasma levels of GDF15 and TGFβ2 were measured by ELISA. Pulmonary fibrosis was evaluated by CT density scan 3 and 12 monthsafter RT.

Results: All patients showed elevated GDF-15 protein levels 3 weeks after RT. In 76% of the patients the increased GDF-15 level persisted for 21 weeks after therapy. The plasmalevel of TGFwereelevatedin 76 % of patients 3 weeks after radiation, and 43% of the patients showed elevated plasma levels 21 weeks after RT.

Increased CT density was detected in the lung of 13 and 6 patients 3 months and 1 year after RT, respectively. Patients withelevated plasmaGDF-15 levels (16/21) had higher rates of radiation-inducedfibrosis (10/13)than patients with decreased or stable plasmaGDF-15 (3/13) levels.Considering TGFβ2,about 85% of those patients had signs of fibrosis (11/13)who presented persistentlyelevated levels of the protein in their plasma 21 weeks after irradiation. Unchanged level of the examined proteins was found in 14% of the patients with fibrosis.

Conclusions:The data suggest that patients with elevated plasma levels of GDF15andTGFβ2might have higher risks of fibrosis development; however the individual reactions cannot be predicted.

MYELOMA MANAGEMENT IN THE ERA OF NOVEL AGENTSBojan Anca1,2

1) Oncology Institute „Ion Chiricuta”; 2) UMF „Iuliu Hatieganu”

Multiple myeloma is a neoplastic plasma cell disorder characterised by clonal proliferation of malignant plasma cells in the bone-marrow microenvironment and monoclonal protein in the blood or urine, associated with organ dysfunction: anaemia, renal impairment, hypercalcaemia, bone disease (CRAB criteria).

The incidence of this disease is likely to increase in the near future as the population ages. Lately sensitive tests for diagnosis, prognosis and treatment monitoring have developed for the bone marrow level: molecular cytogenetics, flow cytometry, molecular biology, next generation sequencing, as well as for the outside bone marrow: heavy-light chain, CT and PET.

The introduction of thalidomide, lenalidomide and bortezomib has changed the treatment paradigm and prolonged the survival rates of myeloma patients. Regimens based on bortezomib or lenalidomide followed by autologous stem cell transplantation are recommended for transplantation eligible patients. Combination therapy with melphalan and prednisone plus either thalidomide or bortezomib is suggested in patients who are not eligible for transplantation. Maintenance therapy with thalidomide, lenalidomide or bortezomib improves progression-free survival, but longer follow-up is needed to assess the effect on overall survival.

Novel agents have improved outlook for patients with relapsed disease: proteasome inhibitors - Carfilzomib, approved in the USA, immuno-modulators (IMID) -

Pomalidomide, HDAC inhibitors – Panobinostat or Vorinostat, mTOR inhibitors - Temsirolimus, etc.

NEOADJUVANT CHEMOTHERAPY IN THE TREATMENT OF CERVICAL CANCER: ADVANCES AND CONTROVERSIESNagy Viorica Magdalena1,2

1) University of Medicine and Pharmacy „Iuliu Hatieganu”; 2) Institute of Oncology „Prof.Dr. Ion Chiricuta”

The treatment of cervical cancer has seen great advances in the last fifteen years. In 1999, a National Cancer Institute Alert was issued recommending the incorporation of concurrent (cisplatin-based) chemotherapy in women undergoing RT for the treatment of locally advanced or high-risk cervical cancer. This Alert was followed by meta-analyses in 2001 and 2008 supporting the efficacy of primary chemoRT(CRT). Consequently, for many patients with invasive cervical cancer, concomitant CRT became the new standard of care.

Questions about the best treatment approach are still opened. Controversies about the selection of surgical versus nonsurgical cases are still current such as are the controversial thoughts about neoadjuvant and adjuvant chemotherapy.

Cervical cancer was previously thought to be chemo-resistant, and therefore chemotherapy was used only for recurrent or metastatic disease. However, after responses were noted to platinum-based interest in the use of chemotherapy was reignited, particularly in the neoadjuvant setting.

TREATMENT SESSION II


One of the motivations behind NACT in the treatment of cervical cancer was to reduce tumour size in order to facilitate surgical resection. A systematic review and meta-analysis, in 2010 was published, examining the role of NACT in women with cervical cancer. Six trials were included, with a total of 1072 women with FIGO stage IB – IIIB disease. All trials used cisplatin-based chemotherapy. The authors found that NACT prior to surgery resulted in an improved progression-free survival (HR = 0.76, 95% CI 0.62 – 0.94, p = 0.01). However, there was no difference in overall survival (HR = 0.85, 95% CI 0.67 -1.07, p = 0.17).

The use of NACT prior to radiotherapy was introduced in order to attempt improved survival in patients with locally advanced cervical cancer. The objective of NACT, therefore, was to eradicate subclinical distant metastases and to improve the local disease control by achieving a reduction in tumour size. Theoretical benefits to NACT prior to RT include increased radiosensitivity and decreased hypoxic cell fractions with tumour size reduction, improved drug delivery and distribution to the tissues prior to radiation vasculitis and possible radiation potentiation using platinum-based regimens.

NACT prior to RT is not supported in the literature, and at present should only be considered in the setting of clinical trials where comparisons are made with the current standard treatment using concurrent CRT protocols.

TNF SIRNA AS MODULATORS OF APOPTOSIS AND ANGIOGENESIS, IN CELL MIGRATION AND INVASION IN TRIPLE NEGATIVE BREAST CANCER CELLS (TNBC)Ioana Berindan Neagoe1,2, Valentina Pilecki2, Roxana Cojocneanu Petric2,3, Laura Pop2, Cornelia Braicu1,2

1) University of Medicine and Pharmacy „Iuliu Hatieganu” Cluj Napoca - The Research Center Functional Genomics Biomedicine and Translational Medicine; 2) The Oncology Institute Ion Chiricuta Cluj Napoca; 3) University Babes Bolyai Cluj Napoca - Faculty of Biology

Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been linked to breast cancer development. Estrogen metabolic pathway is also involved in breast carcino-genesis and DNA adducts formation. A particular case is the TNF- α modulation in TNBC ( triple negative breast cancer). Currently there are several TNF-α antagonists applied in clinical use and these agents have provided significant benefits for a variety of cancers. In the last years a special interest have received triple negative breast cancer which is a highly aggressive subtype that observed particularly in young patients with a poor overall survival

rate and no target therapy. In our experiments, we used as an in vitro model for triple negative breast cancer - the cell line Hs578T - for evaluation of gene expression profiling of signaling networks involved in apoptosis using PCR-array genes. Treatment with special designed siRNA molecules to target TNF-α mRNA has been done for angiogenesis modulation and most relevant genes were evaluated by qRT-PCR.

Knockdown of TNF-α gene was connected with activation of apoptosis processes and inhibition of cell migration and invasion, as monitored using the xCELLigence RTCA System and by in vitro matrigel angiogenesis assay.

There are down-regulated genes involved in cell survival and angiogenesis, whereas the up-regulated ones with pro-apoptotic role.

TFN-α represents a central molecule in the modulation of processes, apoptosis and angiogenesis. TFN-α gene silencing offers an alternative therapeutic strategy in triple negative breast cancer.

LOCAL EXPERIENCE IN THE CLINICAL SET-UP OF TRANSRECTAL ULTRASOUND AND MAGNETIC RESONANCE IMAGING IN ADVANCED CERVICAL CANCERClaudia Ordeanu1, Radu Badea2,3, Csaba Csutak4, Diana-Cristina Pop1, Reka Kerekes5, Viorica Nagy1,3

1) Instututul Oncologic „Prof. Dr. Ion Chiricuta”, Cluj-Napoca; 2) Institutul Regional de Gastroenterologie si Hepatologie „Prof. Dr. O. Fodor”, Cluj-Napoca; 3) Universitatea de Medicina si Farmacie „Iuliu Hatieganu”, Cluj-Napoca; 4) Centrul Medico-Chirurgical Universitar Interservisan, Cluj-Napoca; 5) Spitalul Clinic Judetean de Urgenta, Cluj-Napoca

Objective: The aim of this study was to analyze the accuracy of transrectal ultrasound (TRUS) in comparison to magnetic resonance imaging (MRI) and clinical estimation, in the evaluation of tumor dimensions, parametrial infiltration and identification of residual tumor in advanced cervical cancer.

Methods: Patients underwent clinical, TRUS and MRI examination prior to external beam radiotherapy (EBRT) and prior to the first fraction of brachytherapy (BT). Each examination was performed by a different physician without any knowledge about the patients clinicopathological details. Univariate analysis were performed to identify the prognostic significance of the tumor volume.

In the evaluation procedure the dimensions of the tumor were compared: CC (cranio-caudal), AP (anterior-posterior) and LL (latero-lateral).

Results: Between January – August 20013, 28 patients


with advanced cervical cancer (II-IIIB) were included in this study; for 4 patients we compared the clinical findings vs. TRUS vs. MRI prior to EBRT and prior to BT; 8 patients underwent only prior to the EBRT the comparison between the clinical findings vs. TRUS vs. MRI and for the 16 remaining patients we compared only the clinical findings to MRI.

Conclusions: In patients with advanced cervical cancer, MRI is superior to TRUS and clinical examination for evaluating tumor size. TRUS has the advantages over MRI of low costs, wide spread availability and of being a relative quick procedure; despite this MRI is a non- invaziv imaging modality.

TREATMENT SESSION III

RISK FACTORS AND LONG TERM SURVIVAL IN GERM CELL TUMORS STAGE I

Cristina Ligia Cebotaru, Nicoleta Zenovia Antone, Monica Groza, Nicolae Todor, Maximilian Hogea

Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca

Objective: evaluation of treatment and risk factors for relapse for germ cell tumors stage I.

Material and methods: retrospective study evaluated 253 patients aged between 14 and 78 years (medium age- 33,9 years) germ cell testicular stage I between January 1982-January 2007, treated at the Ion Chiricuta Cancer Center, Cluj-Napoca. The medium follow-up period was 126 months (range minimum 3 month-maximum 285 months). Demographic, clinical and paraclinical parameters of patients were observed.

The histological classification consisted of 126 patients with seminoma (50%), the rest nonseminoma (choriocarcinoma, embryonal carcinoma, Yolk sac tumor, teratoma and malignant mixed germ cell tumor).

Chemotherapy regimens administered in adjuvant setting were Carboplatin AUC 7 for stage I seminoma, EP and BEP for nonseminoma. VAB6 protocol was used before the BEP era.

Results: Overall survival at 10 years was 93% (CI: 89%-96%).

Ninety nine seminoma patients (78,57%) presented relapse, metastatic relapse was observed at 5 patients (3,97%), pelvic or lumboaortic lymph nodes was present at 19 patients (15,08%), metastatic and adenopathy relapse at 2 patients (1,59%) and seric relapse at 1 patient(0,79%). For nonseminoma patients the relapse was present at 11 patients (8,66%).

Risk factors evaluated for relapse were age at presentation (p=0,1), performance status(p<0,1), stage of disease at presentation(p<0,1) and presence of markers(p=0,1).

Chemotherapy toxicity were moderate, main toxicity for Carboplatin was thrombocytopenia (6,67%), for BEP protocol was leucopenia (4,76%), anemia(4,76%) and nausea and vomiting (11,9%).

Our results are superposable with literature dates. Conclusion: Germ cell tumor prognostic is excellent.

The rate of curability for adjuvant treatment is high, the overall survival at 10 years is 93% (CI: 89%-96%).

SHOULD BE THE IMMEDIATE SILICONE BREAST IMPLANTATION IN BREAST CANCER PATIENTS POSTPONED AFTER PERFORMING THE EXTERNAL BEAM RADIOTHERAPY?Chiricuta IC

AMETHYST Radiotherapy Center -Otopeni

Introduction: theimmediate breast reconstruction using silicone implant or autologous tissue transplant is presently a common procedure in breast cancer patients. The item of this presentation is to evaluate our experience with breast cancer pacients with immediate silicone breast implantation who were refered and were irradiated at our center.

Methods:we analysed all 14 patients who were refered to our center in the last year after immediate breast reconstruction for postoperative radiotherapy. The TNM classification of all these patients and the indications for immediate silicone or reconstruction with autologous tissue were analysed. A postoperative radiotherapy using the


VMAT intensity modulated radiotherapy was applied to all 10 patients treated at our center.

Results:The complete treatment planning procedure starting with the clinical target volume delineation (CTV), the planning target delineation (PTV) and the quality of the final dose distribution was analysed. The inclusion of the locoregionallymphatics as the axillary, internal mammary and/or the supraclavicular lymph nodes depended on the results of the pathological examination. The acute and late side effects were recorded.

Conclusion:to obtain an adequate tumor control and to reduce the late side effects we recommend to performe the breast reconstruction using the silicone implant after the delivery of the postoperative radiotherapy.

UPDATE ON BREAST RECONSTRUCTION TECHNIQUES AND INDICATIONS

Andrei Martin

Plastic surgeon, Clinica MEDESTET

Breast reconstruction is considered as part of the breast cancer treatment when breast “mutilating” surgical treatment is required. Numerous publications confirm the psychosocial benefit resulting from the breast reconstruction. Oncoplastic surgery procedures can improve the cosmetic results of the conservative surgery, also extending its indications and reducing both mastectomy and reexcision rates.

Radiotherapy is proposed after conservative surgery as well as in case of positive lymph node metastases after mastectomy, raising the discussion about the technique choice and the timing of the reconstruction.

Skin sparing mastectomy and immediate breast reconstruction became very popular in the last decade, due to both, patients and the reconstructive surgeons: strong psychological impact, saving time and money and obtaining a superior aesthetic result.

Implants or expanders are the most popular techniques used for the reconstructions. Autologus reconstructions using musculocutaneous flap, such as rectus abdominis, or latissimus dorsi autologous flaps eliminates the risks and complications associated with “foreign body” material.

When microsurgical facilities are available, free flaps (like TRAM, S-GAP) or perforator flaps (DIEP flap) respecting the muscle are preferred to decrease the donor site complications.

The nipple areola complex, which can be preserved in certain conditions, can be reconstructed in a second stage under local anesthesia.

There remains controversy as to whether immediate breast reconstruction with postoperative radiotherapy is associated with acceptable complications and aesthetic

outcomes, as well as with delayed breast reconstruction following post-mastectomy irradiation.

RADIOTHERAPY AND BREAST RECONSTRUCTION: TIMING AND CLINICAL OUTCOMES. RADIATION ONCOLOGIST POINT OF VIEWDaniela Martin, Dan Dordai, Gabriela Tufăscu, Carmen Popa, Radu Tănăsescu

Institute of Oncology “Ion Chiricuta” Cluj Napoca

Many patients choose immediate reconstruction after mastectomy to handle with the psychological and esthetic consequences after radical surgery. The presence of a breast reconstruction is a challenge for radiation oncologist, because of the dosimetric and the planning issues. Most of the literature regarding the use of reconstruction with

postmastectomy radiotherapy (PMRT) is retrospective and limited by small patient numbers, short follow-up or heterogeneity with regard to the timing/ techniques of reconstruction and PMRT schedules. Many studies also report conflicting outcomes, especially with respect to tissue expander or implant reconstruction and radiation therapy.

This article purpose is to determine the clinical impact of this increasing use of PMRT postmastectomy radiation therapy in patients with breast cancer who desire implant-based breast reconstruction.

The most frequently reported complications in patients with tissue expander/ implant reconstruction are: capsular contracture (CC), infection and rupture. Implant failure is defined as removal of the implant or replacement with another reconstruction.

There was no evidence that either chemotherapy or hormonal therapy influenced the development of severe CC. These results may influence women who will require postoperative RT to prefer totally autologous reconstructions, and may also influence the decision whether to give postoperative RT in cases at intermediate risk of loco regional recurrence.

Multidisciplinary coordination between the plastic surgeon and the medical and radiation oncologist is essential for achieving consistency.

THE TREATMENT PLANNING USING VMAT FOR IMMEDIATE SILICONEIMPLANT BREAST RECONSTRUCTIONR. Popa, V. Ciocaltei, M. Suditu, D. Adam

Amethyst Radiotherapy Center, Otopeni, Romania


Introduction:External beam radiation therapy (RT) is often used to treat breast cancer patients after mastectomy followed by immediate siliconebreast reconstruction. We evaluated 10 pacients with immediate silicon breast implantation refered to our center for postoperative radiotherapy.

Methods: All pacientsafter performing a CT planning (Phylips Big Bore 120 CT Simulator) were irradiated based on a intensity modulated technique, in our case VMAT. The treatment planning included the clinical target volume (CTV), the planning target volume (PTV) and the boost target volume as well as all organs at risc as the lung tissue, the esophagus, the contralateral breast and the myocard. Treatment planning was performed by a Pinnacle3 System, vers.9.4. All treatment plans were verified by the Octavius 4D phantom before the first irradiation. The patients were treated using a double arc of 6 MV, delivered by Elekta Synergy Linac. The recommendations of the ICRU 83 tried to be fullfiled.

Results: The evaluation of all patients treated using a double arc VMAT technique (ELEKTA Sinergy 6Mev accelerator) was performed. Special attention was given to the dose delivered at the subcutaneous tissue at the anterior part of the silicone implant and at the level of the posterior part to the silicon implant tissue those places were the local recurrences could be manifest. The dose volume histograms (DVH) and the dose distribution have been analyzed in order to identify regions that are under dosed or over dosed (cold and hot spots). Special attention was given to the build up region at the surface of the implant.

Conclusions:The optimisation of the delivery of the prescribed dose (50,4 Gy/1,8 or 50 Gy/2 Gy fractions) to the anterior part of the CTV is a challenge for the treatment planning process, being known the problems encountered in the buld-up regions.

Achimaş-Cadariu Patriciu 23Adam D. 45Aldea Mihaela 31, 32Alexa Teodora 35Amateau Staurt 30An Fangmei 30Antone Nicoleta Zenovia 20,44Avram Mariana 37Badea Radu 42Bako Margareta 19Berindan-Neagoe Ioana 24,31,32,33,42Bly R. 28Bochis Sorin 37Bogdan Victor 17,19Bojan Anca 41Bosteanu Carmen 35Braicu Cornelia 32,33,42Braicu Ovidiu-Leonard 32Brie Ioana-Carmen 25Buiga Rares 24Bulot M 28Campian Corina 19Catau Gabriela 34,37,38Cebotaru Cristina Ligia 20,44Cernea Dana 17,19Cernea Valentin 17Chiricuta IC 44Chis A. 36Chis Octavian 17, 20 Ciocaltei V. 45Ciuleanu Elisabeta 17Ciuleanu Tudor Eliade 17,24Clement Dana 39Cocea Corina 39Cojocneanu Petric Roxana 32,33,42Constantin Teodor Ionut 38,39

Coza Daniela 22,23Cristea Victor 31Csutak Csaba 42Cucuianu Andrei 33Custura Elisabeta 19David Anca 37Dirk Rades 28Ditoiu Alecse Valerian 38,39Dordai Dan 45Florian Ioan Stefan 32Gafton Bogdan 39Gheorghiu Danut 17Gherman Claudia 33Giorgiades Christos 30Godet JL 28Grecea Daniela 19 Grosu Anca-Ligia 25Groza Monica 20,44Guedea Ferran 27Halaşag Silviu 17,19Hegyesi Hargita 40Hogea Maximilian 44Irimie Alexandru 23,31,32Ishida Masaharu 31Jahnen A 28Jarvinen H. 28Kacso Gabriel 19,20,31,32Kahán Zsuzsanna 40Kalloo Anthony 30Kerekes Reka 42Khashab Mouen 30Krengli M 28László Istvan 19,20Li Ling 30Lisencu Carmen 26Lovasz Lidia 22

INDEXUL AUTORILOR


Maingon P 28Malicki J. 28Mandea V. 36Martin Andrei 45Martin Daniela 45Marton AnnaMaria 22Marusteri Mariana 38Mezey Esteban 30Mintoiu Corina Georgiana 38,39Miron Lucian 35,39Murgulet Elena 39Nagy Viorica 18,41,42Neamţiu Luciana 22,23Nemes Adina 18Nicula Florian 22,23Olinici D.Corneliu 24Ordeanu Claudia 42Patcas Diana 20Patrulescu Andreea 19Pawlik Timothy 30Peng Haoran 31Petrushev Bobe 31,32Pileczki Valentina 32,33,42Ples Horia 34,37Ples Stanca Mihaela 34,37Pop Diana 19Pop Diana-Cristina 42Pop Laura 32,33,42Popa Carmen 45Popa R. 45Popiţa Cristian 26Popiţa Raluca 26Popita Vasile 17

Postolache Eva Maria 39Pötter Richard 27Prieto Martin C 28Pruteanu Cristina 39Przybylska K 28Resiga Liliana 17Sáfrány Géza 40Sándor Nikolett 40Schilling-Tóth Boglárka 40Selaru Florin 30, 31Sipos Anamaria 19,20Sirbu Mihaela 22Skrobala A 28Soritau Olga 31,32Stăhiescu Raluca 17,19Suditu M. 45Şuteu Ofelia 22,23Taflan C. 36Tănăsescu Radu 45Todor Nicolae 17,19,20,44Tohanean Dobre Mihaela 38,39Tomuleasa Ciprian 30,31,32,33Tufăscu Gabriela 45Turdeanu Cristian 17Udrea Adrian 37Umegaki Sho 30Valero M 28Varga Zoltán 40Varlan Ancuta 35Virtic Oana 33Volovat Simona 35Yamanaka Sumitaka 30,31

the 23 · current concepts and clinical evidence in image guided adaptive brachytherapy of cervical...

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