National Cancer Institute (Slovakia)

Salmanton-Garcia J., Marchesi F., Labrador J., Fracchiolla N., Bilgin Y.M., Del Principe M.I., Drgoňa Ľ., Rahimli L., Plantefève G., Van Praet J., Sgherza N., Piukovics K., Espigado I., Fernando I.H., Cornely O.A., et. al.

Abstract Background With growing concerns about the effects of community-acquired respiratory viruses (CARVs) on hematological malignancy patients, proactive measures are necessary to minimize risks and improve treatment results. This study aimed to collect and analyze epidemiological, management, and outcome data from these patients with CARV infections to develop customized clinical management approaches.Table 1.Patient characterisitics Methods Utilizing an online registry, data from of CARV infections in hematological malignancy patients were collected from January 2023 to January 2024, spanning 53 sites across 21 countries. Results Our survey included 561 cases of CARV in hematological malignancy patients, with a majority from Italy (39%) and Spain (19%). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made up 63% of cases, followed by influenza (15%), respiratory syncytial virus (12%), and rhinovirus (9%). The distribution of CARVs mirrored the overall prevalence across different malignancies, with 27% in acute leukemias and non-Hodgkin lymphoma each, and 21% in multiple myeloma. Stem cell transplantation or CAR-T therapy preceded CARV infection in 24% of patients, particularly with metapneumovirus (67%) and parainfluenza (60%). Chronic cardiopathies were the most common comorbidity (41%). Critical illness was more prevalent in metapneumovirus (22%) and influenza cases (18%) compared to RSV (11%) or SARS-CoV-2 (8%). Metapneumovirus and parainfluenza had the highest mortality rates (33% and 30%, respectively), surpassing those of influenza (16%) or SARS-CoV-2 (11%). SARS-CoV-2 (68%) and RSV (50%) had the highest associated mortality rates. Progression of baseline malignancy contributed to 50% of overall mortalities. Further details are provided in Table 1. Conclusion Our study underscores the significant impact of CARV on hematological malignancy patients, especially with SARS-CoV-2 predominance. The distribution of CARVs reflected malignancy prevalence, with acute leukemias and non-Hodgkin lymphoma most affected. Moreover, we found heightened severity and mortality rates associated with specific CARV pathogens such as metapneumovirus and parainfluenza. Disclosures Oliver A. Cornely, Prof. Dr., Abbott: Honoraria|Abbvie: Advisor/Consultant|Abbvie: Honoraria|AiCuris: Advisor/Consultant|Akademie fur Infektionmedizin: Honoraria|Al-Jazeera Pharmaceuticals/Hikma: Honoraria|amedes: Honoraria|AstraZeneca: Honoraria|Basilea: Advisor/Consultant|Biocon: Advisor/Consultant|BMBF: Grant/Research Support|Boston Strategic Partners: Advisor/Consultant|CIdara: Advisor/Consultant|CIdara: Expert Testimony|CIdara: Grant/Research Support|CIdara: Participation on a DRC or DSMB|CoRe Consulting: Stocks/Bonds (Private Company)|Deutscher Arzteverlag: Honoraria|DZIF: Grant/Research Support|EasyRadiology: Stocks/Bonds (Private Company)|EU-DG RTD: Grant/Research Support|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Grupo Biotoscana/United Medical/Knight: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|IQVIA: Advisor/Consultant|IQVIA: Participation on a DRC or DSMB|Janssen: Advisor/Consultant|Janssen: Participation on a DRC or DSMB|Matinas: Advisor/Consultant|MedPace: Advisor/Consultant|MedPace: Grant/Research Support|MedPace: Participation on a DRC or DSMB|Medscape/WebMD: Honoraria|MedUpdate: Honoraria|Menarini: Advisor/Consultant|Moderna: Honoraria|Molecular Partners: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|MSG-ERC: Advisor/Consultant|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Mundipharma: Honoraria|Noscendo: Honoraria|Noxxon: Advisor/Consultant|Octapharma: Advisor/Consultant|Octapharma: Grant/Research Support|Pardes: Advisor/Consultant|Partner Therapeutics: Advisor/Consultant|Patent: US18/562644|Paul-Martini-Stiftung: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|PSI: Advisor/Consultant|PSI: Participation on a DRC or DSMB|Pulmocide: Participation on a DRC or DSMB|Sandoz: Honoraria|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Seqirus: Advisor/Consultant|Seqirus: Honoraria|Seres: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria|streamedup!: Honoraria|The Prime Meridian Group: Advisor/Consultant|Touch Independent: Honoraria|Vitis: Honoraria

Amiri A., Slobodová L., Klepochová R., Schön M., Marček Malenovská K., Rerková K., Pechancová R., Prievalský M., Litváková V., Oliva V., Pluháček T., Sedliak M., Mego M., Krššák M., Chovanec M., et. al.

AbstractBackgroundPlatinum‐based chemotherapy provides curative treatment to more than 95% of patients with testicular germ cell tumor but it has negative cardiometabolic and neurological effects. Regular exercise can alleviate late chemotherapy‐related toxicities. We examined the impact of a 6‐month supervised aerobic‐strength training on cognitive and cardiometabolic health and residual level of platinum in cancer survivors.MethodsTwenty‐eight middle‐aged (42.1 ± 7.6 years) testicular germ cell tumor survivors subjected to platinum‐based chemotherapy (1–8 cycles, 0–24 years ago) were recruited into exercise (n = 20) and control (n = 8) groups. Effects of 6‐month exercise training on the whole‐body and muscle metabolism, cognitive functions, cardiopulmonary fitness, residual plasma platinum, and plasma adiponectin were examined.ResultsExercise intervention improved cardiopulmonary fitness and cognitive functions, reduced residual plasma platinum, visceral adiposity and muscle lipids, improved glucose (glycosylated hemoglobin) and lipid (high‐density lipoprotein cholesterol) metabolism, and enhanced dynamics of muscle post‐exercise phosphocreatine recovery. Exercise‐related decline in plasma platinum was paralleled by decline of muscle glycerophosphocholines and by the enhanced metabolic flexibility during low‐intensity exercise, and predicted training‐induced increase in cognitive functions.ConclusionsThe 6‐month exercise intervention resulted in improved cognitive and cardiometabolic health in testicular germ cell tumor survivors, which was paralleled by reduced plasma platinum, providing evidence that structured supervised exercise brings multiple health benefits to testicular germ cell tumor survivors.

Ciernikova S., Sevcikova A., Novisedlakova M., Mego M.

Immunotherapy with immune checkpoint inhibitors represents a revolutionary approach to the treatment of solid tumors, including malignant melanoma, lung cancer, and gastrointestinal malignancies. Anti-CTLA-4 and anti-PD-1/PDL-1 therapies provide prolonged survival for cancer patients, but their efficacy and safety are highly variable. This review focuses on the crucial role of the gut microbiome in modulating the efficacy and toxicity of immune checkpoint blockade. Studies suggest that the composition of the gut microbiome may influence the response to immunotherapy, with specific bacterial strains able to promote an anti-tumor immune response. On the other hand, dysbiosis may increase the risk of adverse effects, such as immune-mediated colitis. Interventions aimed at modulating the microbiome, including the use of probiotics, prebiotics, fecal microbial transplantation, or dietary modifications, represent promising strategies to increase treatment efficacy and reduce toxicity. The combination of immunotherapy with the microbiome-based strategy opens up new possibilities for personalized treatment. In addition, factors such as physical activity and nutritional supplementation may indirectly influence the gut ecosystem and consequently improve treatment outcomes in refractory patients, leading to enhanced patient responses and prolonged survival.

Salmanton‐García J., Marchesi F., Navrátil M., Piukovics K., del Principe M.I., Criscuolo M., Bilgin Y.M., Fracchiolla N.S., Vena A., Romano A., Falces‐Romero I., Sgherza N., Heras‐Fernando I., Biernat M.M., Petzer V., et. al.

ABSTRACTCommunity‐acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large‐scale, real‐world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA‐EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. The study assessed epidemiology, clinical characteristics, risk factors, and outcomes. The study examined 1312 patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. Of these, 59.5% required hospitalization, with 13.5% needing ICU admission. The overall mortality rate was 10.6%, varying by virus: parainfluenza (21.3%), influenza (8.8%), metapneumovirus (7.1%), RSV (5.9%), or SARS‐CoV‐2 (5.0%). Poor outcomes were significantly associated with smoking history, severe lymphopenia, secondary bacterial infections, and ICU admission. This study highlights the severe risk CARV poses to patients with HM, especially those undergoing active treatment. The high rates of hospitalization and mortality stress the need for better prevention, early diagnosis, and targeted therapies. Given the severe outcomes with certain viruses like parainfluenza, tailored strategies are crucial to improving patient outcomes in future CARV seasons.

Boča R., Štofko J., Ladická M., Rajnák C.

Rusnáková D., Aziri R., Dubovan P., Jurík M., Mego M., Pinďák D.

Cingelova S., Mikuskova E., Demitrovicova L., Mikudova V., Slobodova A., Spanikova J., Vasickova R., Urban D., Drgona L., Oravcova I.

In acute promyelocytic leukemia (APL), the combination treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) appears to have a synergistic effect. Due to this synergism, differentiation syndrome (DS) in APL assumes a distinct identity separate from the formerly known ATRA syndrome, with distinct temporal patterns, diagnostic parameters, and clinical behavior. We retrospectively evaluated single-center data of years 2013-2022. Patients with newly diagnosed APL were categorized into three groups (16 patients in ATRA/ATO standard-risk group, 3 patients in ATRA/chemotherapy standard-risk group, and 5 patients in ATRA/chemotherapy high-risk group). Our aim was to analyze leukocytosis, signs of DS, and hepatic impairment within the first 25 days of treatment. The incidence of DS in the ATRA/ATO SR group was 43.8 %, with a median of 4 days and 2 days from ATRA and ATO initiation, respectively. This group also exhibited higher peak levels of leukocytosis 34.5 (6.0-113.4) x10

Cavalli C., Gusmaroli E., Taglialatela I., Mego M., Bimbatti D., Secondino S., Biasoni D., Catanzaro M., Claps M., Zimatore M., Torelli T., Stagni S., Macchi A., Tesone A., Pedrazzoli P., et. al.

Primitive Retroperitoneal Germinal Cell Tumors (pR-GCT) corresponds to the clinical case of retroperitoneal ascertained GCT without evidence of primary testicular tumor and accounts for up to 40 % of extragonadal GCTs. An occult primary testicular tumor is often missed at diagnosis. Treatment modalities and outcomes have not been specifically addressed, preventing robust recommendations. We performed an international call to assess prognosis of treatment outcomes of these pts. Clinical, pathological and treatment data pts with pR-GCT between April 1988 and January 2022 were retrospectively collected across four referral centers. Kaplan Meier methods, univariable and multivariable Cox regression models (MCRMs) were used. Ninety-nine pts (median age 37 years - IQR: 29-45) were collected. Ninety-three (94%) had histological diagnosis by biopsy or primary retroperitoneal lymph-node dissection: 60 (62.5%) had non-seminomatous (pR-NSGCTs) and 33 (34.4%) had seminomatous (pR-SGCTs). IGCCCG prognostic allocation was possible in 91 pts: 34 (35.8%) were good, 23 (24.2%) intermediate and 34 (35.8%) poor-risk, respectively. All pts underwent cisplatin-based chemotherapy, usually BEP (94.9%). After chemotherapy, 25 (25.3%) pts underwent orchiectomy: viable tumor was present in 8 (32%), burn-out lesions in 6 (24%) and no lesion in 11 (44%). After a median FUP of 45 m (IQR:15-90), the 5-yrs OS was 58%, being 85% in case of pR-SGCT and 46% in case of pR-NSGCT. According to IGCCCG classification 5-yrs OS was 83.3% for good, 57% for intermediate, 42% for poor-risk pts, respectively. No difference in term of OS (60% vs 56%, p-value 0.81) was observed between patient who had or not radical orchiectomy. At MCRMs only IGCCCG poor risk category (HR 3.2, CI: 1.18-8.84, p-value 0.02) was independent predictor of a worse OS. Eventually, a significant proportion of patients with pR-GCT had a misclassified primary testicular tumor. 5 years-OS according to IGCCCG-classification is worse than expected. The role of a surgical exploration of the suspected primary tumor remains controversial and the existence of a real category of p-RGCT cannot be excluded.

Kunová A., Trupl J., Špánik S., Drgoňa L., Šufliarsky J., Lacka J., Studená V., Hlaváčová E., Studená M., Kukučková E., Kollár T., Pichňa P., Oravcová E., Krčméry, Jr. V.

During the 5-year period 1989-1993, the incidence of Candida krusei, and other non-albicans Candida spp., was analyzed in a 60-bed cancer department. The frequency of C. krusei, before fluconazole was introduced into therapeutic protocols in 1990, was 16.5%, and after introduction of fluconazole into prophylaxis in acute leukemia in 1991, the incidence of C. krusei was 12.7%. After 3 years of using this drug in therapy and prophylaxis, the incidence of C. krusei in 1993 was 14.8%, what was lower than before this drug was introduced in our country. 97.6% of all isolated fungi were yeasts and only 2.4% were molds. Among yeasts, the most frequently isolated pathogen was Candida albicans with 64.3% in 1989 and 74.2% in 1993. The next was C. krusei with 21.2% in 1992 and 16.5% in 1989, but 14.8% in 1993, and Candida tropicalis and Candida glabrata with 9.03% in 1989 and 2.7% in 1993. Among the molds, Aspergillus spp. was the most frequently isolated genus. Analyzing the etiology of mycologically proven fungal infections confirmed by positive blood cultures or biopsies, C. albicans and Aspergillus spp. were the most common causative organisms.

Krčméry,.Jr. V., Fuchsberger P., Trupl J., Šufliarsky J., Španik S., Koza I., Kusenda Z., Korec S., Švec J., Ďurkovič P., Lakota J., Horníková M.

58 granulocytopenic patients with confirmed bronchopneumonia were divided retrospectively into two groups for this pilot study: group 1 included neutropenic patients with venous catheters who were treated with ciprofloxacin (CIP; 200-300 mg, i.v. b.i.d.) + vancomycin (VAN; 0.5-1 g, i.v. b.i.d.), and group 2, which included patients without venous catheters treated with ceftazidime (2 g, i.v. t.i.d.) + gentamicin (1 mg/kg, i.v. t.i.d.). Pneumonia was diagnosed clinically and radiologically in all patients; 92.3% in group 1 and 46.8% in group 2 were also microbially confirmed. Mixed infections were present in most patients. 3 of 26 patients (11.5%) in group 1 and 9 of 32 (20.1%) in group 2 did not recover while 88.5% in group 1 and 71.9% in group 2 recovered. CIP + VAN seems to be more effective in treating pneumonia in neutropenic patients, with only 1 patient in the group suffering an adverse effect compared with 5 in group 2.

Krčméry, Jr. V., Koza I., Mardiak J., Fuchsberger P., Špánik S., Trupl J., Horníková M., Kusenda Z., Šufliarsky J., Švec J.

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a β-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.