Search

Liquid biopsy is becoming an important source of new biomarkers during the treatment of metastatic cancer patients. Using size-based microfluid technology, we isolated circulating tumor cells (CTCs) from metastatic breast cancer patients to evaluate their presence and cluster formation, as well as the presence of megakaryocytes and immune-inflammatory blood cells, and to correlate their presence with clinicopathological data and overall survival (OS). In total, 59 patients (median age 60.4 years) were included in the study: 62.7% luminal A/B-like, 20.3% HER2-positive, and 17% triple-negative. Our results showed that at least one CTC was present in 79.7% and ≥5 CTCs in 35.2% of the patients. CTC clusters were present in patients with ≥5 CTCs only (in 19.2% of them), and megakaryocytes were present in 52% of all patients. The presence of CTC clusters and megakaryocytes was positively associated with the CTC count. Patients with low pan-inflammatory value (PIV), low systemic immune-inflammatory index (SII), and low relative change from baseline (ΔPIV%, ΔSII%) were associated with significantly higher OS than their counterparts. ΔPIV%, the presence of infection in the last month, and a long duration of metastatic disease were identified as independent prognostic factors for OS. The interplay of CTCs, CTC clusters, megakaryocytes, and PIV needs to be further explored.

Bolnike z rakom glave in vratu v zelo dobrem splošnem stanju ob lokalni in/ali regionalni ali oddaljeni ponovitvi lahko zdravimo s kombinacijo citostatikov in tarčnega zdravila (cisplatin, 5-fluorouracil in cetuksimab) v tritenskih ciklusih. Bolnike v slabšem splošnem stanju zdravimo z monoterapijo, ponavadi z metotreksatom, s katerim dosežemo manj odgovorov na zdravljenje in krajše preživetje. Na Onkološkem inštitutu v Ljubljani smo pri bolnikih v slabšem splošnem stanju preizkusili zdravljenje s kombinacijo treh citostatikov (docetaksel 20 mg/m2, cisplatin 20 mg/m2 in 5-fluorouracil 350 mg/m2 intravensko) kot tedensko kemoterapijo. Rezultate smo analizirali retrospektivno. Zdravili smo 15 bolnikov, v starosti 45-78 let (srednja starost 60 let), srednje trajanje spremljanja je bilo 9,5 mesecev. Bolniki so prejeli povprečno 9 (4-15) tedenskih aplikacij kemoterapije. Sedeminosemdeset odstotkov bolnikov je imelo klinično korist zdravljenja (popolni odgovor - 2 bolnika, delni odgovor - 6 bolnikov, stagnacija bolezni - 5 bolnikov).

Vnetni rak dojke (VRD) je redka, vendar zelo agresivna oblika raka dojke. Pri več kot polovici bolnic so ob postavitvi diagnoze prisotni zasevki v pazdušnih bezgavkah, pri tretjini tudi oddaljeni zasevki. Izid VRD je kljub multimodalnemu zdravljenju, ki vključuje sistemsko zdravljenje, operacijo in obsevanje, slab. Bolnice skupine A so bile zdravljene s kemoterapijo po shemi CMF, skupine B z antraciklini (56%), kombinacijo antraciklinov in taksanov (36%) ali CMF (7%). Večina bolnic je imela operacijo (100 vs. 83%) in dopolnilno obsevanje (73 vs. 81% bolnic; skupina A vs. B). Dopolnilno HT je prejelo 7/27 bolnic skupine A oz. 28/31 bolnic skupine B s hormonsko odvisnim VRD (srednje trajanje 5 mes. v skupini A, 44 mes. v skupini B). Srednji čas do ponovitve je bil 16,9 (skupina A) in. 34,2 mes. (skupina B; p=0,01). Srednje celotno preživetje skupine A je bilo 33,8 mes., skupine B pa 56,6 mes. (p=0,06). Bolnice s hormonsko odvisnim VRD, zdravljene z dopolnilno HT, so imele najdaljši čas do ponovitve bolezni (89 mes.) in celotno preživetje (91 mes.). Preživetje brez ponovitve bolezni in celotno preživetje se je od obdobja 1983-87 do 2001-05 podaljšalo, najbolj pri bolnicah s hormonsko odvisnim VRD, ki so prejele dopolnilno HT.

Background: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge. Summary: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions. Key Messages: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings.

Zaviralci od ciklina odvisnih kinaz (CDK)4/6 so relativno nova tar��na zdravila pri raku dojk, ki jih uporabljamo pri hormonsko odvisnem HER-2 negativnem podtipu za bolnice z lokalno napredovalim ali razsejanim rakom. V registracijskih klini��nih raziskavah, kot tudi v vsakodnevni praksi, so se izkazali za u��inkovita zdravila s sprejemljivim varnostnim profilom. V spodnjem prispevku bomo na kratko predstavili u��inkovitost in najpogostej��e ne��elene u��inke zdravljenja z zaviralci CDK4/6 ter ukrepanje ob njihovem pojavu., Onkologija : strokovno-znanstveni ��asopis za zdravnike, Vol. 25 No. 2 (2021)

Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995–2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein–Barr virus (EBV) was performed. Twenty patients (larynx, 12, pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs ≥ 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed, the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.

Background Selective cyclin-dependent kinases 4/6 inhibitors (CDKi) have become the standard of care in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer (ABC). We performed retrospective analysis in patients treated with CDKi in the first year of their routine clinical use in Slovenia. Methods The primary goals were time-to-treatment failure (TTF) and overall survival (OS), analysed via Kaplan-Meier method, the secondary goals were clinical benefit rate (CBR) and safety. Results Overall, 218 patients’ data were evaluated. The median age was 61.8 years (30.6–84.6). The median number of previous ET lines for ABC was 2 (range 0–5). At the time of inclusion, 128 patients (58.7%) had visceral metastases, 45 patients (20.6%) had bone-only disease. At the median follow-up of 15.2 months, disease progressed in 74 patients and 60 patients died. The median TTF was 8.3 months for the whole group, 19.3, 10.3 and 5.5 months for patients treated in the first-, second- and further lines of systemic therapy, respectively. The median OS from the start of CDKi treatment was not reached in any of the groups. CBR was 59.6% for the whole group, 42.7% for further lines of therapy. The most common grade 3/4 adverse event was neutropaenia in 108 patients (49.5%), followed by an increase of hepatic aminotransferases in 13 patients (6.0%). Conclusions Even in the diverse real-world population treatment with CDKi in combination with ET showed clinical benefit, most prominently in the first- and second lines of systemic therapy.

Introduction: Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak. Methods: We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies. Results: By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis. Conclusions: In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally.

BACKGROUND Providing patients with cancer who are undergoing systemic therapy with useful information about symptom management is essential to prevent unnecessary deterioration of quality of life. OBJECTIVE The aim was to evaluate whether use of an app for symptom management was associated with any change in patient quality of life or use of health resources. METHODS Outpatients with early stage breast cancer receiving systemic therapy were recruited at the Institute of Oncology in Ljubljana, Slovenia. Patients who received systemic therapy between December 2017 and March 2018 (control group) and between April 2018 and September 2018 (intervention group) were eligible. All patients received standard care, but only those in the intervention group were asked to use mPRO Mamma, an Android-based smartphone app, in addition. The app supported daily tracking of 50 symptoms, allowed users to grade their symptom severity (as mild, moderate, or severe), and also provided in-depth descriptions and recommendations based on reported symptom level. Patient-reported outcomes in both groups were assessed through the European Organisation for Research and Treatment of Cancer (EORTC) core (C-30) and breast cancer (BR-23) questionnaires, as well as a questionnaire about health resources use. The primary outcomes were the difference in the global quality of life between groups and the difference in summary score of the EORTC C-30 questionnaire between groups after 3 time periods (the first week of treatment, the first treatment cycle, and the entire treatment). The secondary outcome was the use of health resources (doctor visits and hospitalizations) in each time period. Other scales were used for exploratory analysis. RESULTS The mean difference between the intervention group (n=46) and the control group (n=45) in global quality of life (adjusted for baseline and type of surgery) after the first week was 10.1 (95% CI 1.8 to 18.5, P=.02). The intervention group summary scores were significantly higher than those of the control group after the first week (adjusted mean difference: 8.9, 95% CI 3.1 to 14.7, P=.003) and at the end of treatment (adjusted mean difference: 10.6, 95% CI 3.9 to 17.3, P=.002). Use of health resources was not statistically significant between the groups in either the first week (P=.12) or the first treatment cycle (P=.13). Exploratory analysis findings demonstrated clinically important improvements (indicated by EORTC C-30 or BR-23 scale scores)—social, physical, role, and cognitive function were improved while pain, appetite loss, and systemic therapy side effects were reduced. CONCLUSIONS Use of the app enabled patients undergoing systemic therapy for early stage breast cancer to better cope with symptoms which was demonstrated by a better global quality of life and summary score after the first week and by a better summary score at the end of treatment in the intervention group compared to those of the control group, but no change in the use of health resources was demonstrated.

Rak postaja najpogostejša bolezen in tudi najpogostejši vzrok smrti sodobnega človeka. Breme te bolezni se iz leta v leto povečuje. Na račun zgodnjega odkrivanja in učinkovitejšega ter varnejšega zdravljenja pa se izboljšuje tudi preživetje bolnikov z rakom. To povzroča strmo naraščanje števila preživelih od raka, tako da v razvitem svetu predstavljajo okrog 3 % celotne populacije. Preživeli od raka potrebujejo skrbno spremljanje zdravstvenega stanja tudi po končanem onkološkem zdravljenju. Ne sledimo jih le zaradi nevarnosti ponovitve bolezni (lokoregionalne ali oddaljene), temveč tudi zaradi poznih posledic in neželenih učinkov zdravljenja (fizičnih, psihičnih, socialnih) ter povečanega tveganja zbolevanja za drugimi (sekundarnimi) raki. Ozavestiti jih je treba o zdravem načina življenja in zgodnjem odkrivanju sekundarnih rakov ter tudi o poznih posledicah zdravljenja. Za nekatere vrste raka, ki so dedno pogojene, so na voljo metode genetskega testiranja, predvsem pa je bolnike in svojce treba poučiti o presejalnih metodah (npr. mamografija, kolonoskopija). Preživeli od raka tudi pogosteje od ostale populacije zbolevajo za drugimi, nemalignimi obolenji. Ob vse večjem številu preživelih od raka in v času, ko rak postaja kronična bolezen, je nujno, da se v celostno oskrbo poleg onkologa in družinskega zdravnika vključijo tudi strokovnjaki drugih specialnosti, npr. visoko izobražene medicinske sestre, usmerjene v onkologijo, in psihologi. Cancer is a disease with nearly the highest incidence and also the most frequent cause of death in humans today. Cancer burden is getting higher every year. However, due to early detection of cancer, more efficient and less harmful treatment, the survival of cancer patients is improving. Consequently, also the percentage of cancer survivors is significantly on the rise and, in the developed world, this percentage amounts to 3% of total population there. Cancer survivors require careful follow-up also after completed cancer treatment. These patients are not followed up only because of recurrence risk (locoregional or distant recurrence) but also because of late sequelae and undesired effect of treatment (physical, psychological and social) as well as of increased risk for developing secondary cancers. There is an urgent need to make people aware of the importance of healthy lifestyle and of early detection of secondary malignancies as well as of late sequelae of cancer treatment. The patients and their relatives should be informed that, for hereditary cancers, genetic testing is available, while for the detection of other cancers, screening methods (mammography, coloscopy) are used. Cancer survivors more frequently develop other non-malignant diseases. With the increasing number of cancer survivors and considering that cancer is becoming a chronic disease, it is indispensable that the team who is in charge of comprehensive care of cancer survivors includes, in addition to an oncologist and family doctor, also experts of other disciplines, such as nurses specialized in oncology nursing and psychologists.

BACKGROUND/AIM It can be hypothesized that in patients with locally advanced head and neck cancer and prominent cetuximab (CMb)-induced skin rash, immunoradiotherapy would result in a survival advantage over chemoradiotherapy with cisplatin (CP). PATIENTS AND METHODS After a loading dose of CMb, one weekly cycle of CMb and CP concurrently with RT, patients who developed a grade ≥2 rash proceeded with immunoradiotherapy, and those with a grade 0-1 rash had chemoradiotherapy. RESULTS A grade 3-4 allergic reaction to CMb developed in 11/39 (28.2%) patients and further recruitment was stopped. These patients proceeded treatment with CP. In early assessment of skin rash 10/28 patients qualified for chemoradiotherapy and 18/28 patients for immunoradiotherapy. There was no difference in survival between the two groups. CONCLUSION Rate of serious CMb-induced hypersensitivity reactions was unacceptably high. Even though immunoradiotherapy was administered only to the prognostically most favorable group of patients, it resulted in no advantage over chemoradiotherapy.

In this paper, we describe the first practical application of two methods, which bridge the gap between the non-expert user and machine learning models. The first is a method for explaining classifiers’ predictions, which provides the user with additional information about the decision-making process of a classifier. The second is a reliability estimation methodology for regression predictions, which helps the users to decide to what extent to trust a particular prediction. Both methods are successfully applied to a novel breast cancer recurrence prediction data set and the results are evaluated by expert oncologists.

Background. Human epidermal growth factor receptor 2 (HER2) positive breast cancer is an entity with aggressive behaviour. One year of adjuvant trastuzumab significantly improves the disease free survival in the range of 40-50% and reduces the risk of dying from HER2 positive breast cancer by one third. Adjuvant treatment with trastuzumab became available in Slovenia in 2005 and the aim of this study is to explore, if the exceptional results reported in adjuvant clinical trials are achieved also in daily clinical practice. Patients and methods. An analysis of tumour and patient characteristics, type of treatment and outcome (relapse free and overall survival) of 313 patients (median age 52 years) treated at the Institute of Oncology Ljubljana in years 2005-2009 was performed. Results. Median follow-up was 4.4 years. Sixty-one patients relapsed and 24 died. Three and four years relapse free survival was 84.2% and 80.8% and the overall survival was 94.4% and 92.5%, respectively. Independent prognostic factors for relapse were tumour grade (HR 2.10; 95% CI 1.07-4.14; p = 0.031) and nodal stage (HR 1.35; 1.16-1.56; p < 0.0001) and for the overall survival nodal stage only (HR 1.36; 1.05-1.78; p = 0.021). Conclusions. The outcome in patients with adjuvant trastuzumab in daily clinical practice, treated by medical oncologists, is comparable to results obtained in international adjuvant studies.

The purpose of this study was to assess the efficacy and toxicity of docetaxel, cisplatin/5-fluorouracil (TPF) induction chemotherapy and concomitant immunochemoradiotherapy with cetuximab and cisplatin in unresectable head and neck carcinoma.Treatment consisted of TPF induction chemotherapy (docetaxel 75 mg/m(2) day 2; cisplatin, 75 mg/m(2) day 2; and 5-fluorouracil 750 mg/m(2) days 1-4; 4 cycles), followed by radiotherapy (RT) and concomitant weekly cetuximab, (250 mg/m(2), after a loading dose of 400 mg/m(2)) and cisplatin (30 mg/m(2)).Twenty-five of 30 patients completed 4 cycles of induction chemotherapy. Six or more concomitant infusions of cisplatin and cetuximab were administered in 13 of 25 and 18 of 25 patients, respectively. The 2-year locoregional control, disease-free survival (DFS), and overall survival (OS) were 47%, 47%, and 50%, respectively. Patients with grade ≥ 2 skin reaction to cetuximab had a superior outcome.The tested regimen was effective; however, cetuximab and low-dose cisplatin after induction TPF increased the treatment toxicity. A grade ≥ 2 skin rash correlated with improved efficacy.

Equinatoxin II (EqT II) decreases coronary flow in guinea-pig and rat heart. It increases cytosolic Ca2+ activity and is supposed to form cation selective membrane pores. In the present study we tried to evaluate the influence of the L-type Ca2+ channel antagonist nicardipine upon the vasoconstrictory effect of EqT II on coronary vessels in isolated heart of the rat. Coronary flow was measured during the experiment. Ten min after bolus injection of EqT II the coronary flow decreased to 17.2 +/- 4.3% in experiments without nicardipine, and to 39.4 +/- 4.5% in the group with 0.1 microM nicardipine (p0.05). Our results indicate the possibility that L-type Ca2+ channels could be involved in the effects of EqT II on coronary flow in the rat heart.

Background Microinvasive ductal carcinoma in situ of the breast is a rare entity defined as ductal carcinoma in situ with invasive foci measuring no more than 1 mm. In general, the outcome is excellent, similar to ductal carcinoma in situ. We report a patient with breast ductal carcinoma in situ with microinvasion who died eight months after diagnosis due to progression of the disease – liver metastases. This is the first report in the literature of such an aggressive course. Case presentation A 47-year-old Caucasian woman presented with mammographic-detected suspicious microcalcinations in an area of 8.6 x 6 cm. A radical mastectomy with a sentinel lymph node biopsy and immediate breast reconstruction with implant was performed. A histopathological report showed a massive high grade ductal carcinoma in situ, of the solid and comedo type. In one quadrant, some foci of microinvasions of less than 1 mm were present. Tumour margins were free. Isolated tumour cells were found in the sentinel lymph node. Hormone receptors were negative and human epidermal growth factor receptor-2 status was not performed. The patient received no adjuvant systemic therapy. Eight months after the surgery, she died from hepatic failure without known breast cancer progression before. An autopsy revealed diffuse liver metastases with human epidermal growth factor receptor 2-positive, hormone receptor negative breast cancer. Dissemination to other organs was not proven. Conclusion Our patient is a rare case of ductal carcinoma in situ with microinvasion that developed distant metastases very early. In case of multiple foci of microinvasion, besides radical local treatment we suggest considering adjuvant systemic treatment based on biological characteristics since tumour size alone does not predict the prognosis well.