Safety and efficacy of induction immunochemotherapy with rituximab, methotrexate, ifosfamide, and vincristine (R-MIV) in patients with primary CNS lymphoma including recent COVID-19 pandemic experience.

Clinical data on primary central nervous system (CNS) lymphoma (PCNSL) patients is mostly generated from prospective studies, and many frail real-world patients are not included. Recently,the diagnosis and treatment of PCNSL patients was confounded by the COVID-19 pandemic. In particular, treatment with high-dose cytarabine was linked to increased risk of pneumonia and virus persistence. We report on outcome of the induction regimen R-MIV (rituximab, methotrexate, ifosfamide, and vincristine) involving intensive administration of high-dose methotrexate (3.5 g/m2 ) with ifosfamide, every 2 weeks and rituximab once per week for six doses. The median age and performance status (PS) for 64 patients was 58 years and 2 (PS 3; 22%) respectively. The overall response rate by magnetic resonance imaging/computed tomography (MRI/CT) was 73% (n = 46/63), with an additional 17.5% (n = 11/63) patients without measurable disease at baseline. Grade 3-4 haematological toxicity was low for R-MIV (neutropenia: 25% and thrombocytopenia: 1%). Three patients (4.7%) died from treatment-related toxicity. Co-existence of SARS-CoV-2 infection with cytomegalovirus reactivation and the varicella-zoster virus in two patients was fatal. Fifty patients (78%) were eligible for consolidation. Median progression-free and overall survival were not reached (median follow-up: 44 months). In conclusion, the R-MIV regimen is feasible in routine practice, effective and safe, even during the COVID-19 pandemic.

High efficacy of intensive immunochemotherapy for primary mediastinal B-cell lymphoma with prolonged follow up.

Primary mediastinal B-cell lymphoma (PMBL) is currently curable in 85-95% of patients. Treatment regimens frequently used include RCHOP ± radiotherapy, DAEPOCH-R, or occasionally more intensive protocols. Here we present results of treatment of 124 patients with PMBL over a period between 2004 and 2017 with the use of a protocol designed for aggressive B-cell lymphoma GMALL/B-ALL/NHL2002 including 6 cycles of alternating immunochemotherapy with intermediate-dose methotrexate in each cycle, and reduced total doxorubicin dose (100 mg/m2 for whole treatment). Majority of patients (77%) received consolidative radiotherapy. A median (range) age of patients was 30 (18-59) years, and 60% were female. With a median (range) follow up of 9 (1-17) years, 5-year overall survival (OS) and 5-year progression free survival (PFS) were 94% and 92%, respectively. Positron emission tomography-computed tomography (PET-CT) results at the end of chemotherapy were predictive for outcome: OS and PFS at 5 year were 96% and 94% in PET-CT negative patients, respectively, and 70% and 70% in PET-CT-positive patients (p = 0.004 for OS, p = 0.01 for PFS). Eight (6%) patients had recurrent/refractory disease, however, no central nervous system (CNS) relapse was observed. Acute toxicity included pancytopenia grade 3/4, neutropenic fever, and treatment related mortality rate of 0.8%. Second malignancies and late cardiotoxicity occurred in 2.4% and 2.4% of patients, respectively. Intensive alternating immunochemotherapy protocol GMALL/B-ALL/NHL2002 is curative for more than 90% of PMBL patients and late toxicity in young patients is moderated. The attenuated dose of doxorubicin and intermediate dose of methotrexate may contribute to low incidence of late cardiotoxicity and effective CNS prophylaxis.

Identification of the Optimal Cut-Off Value of PSA for Assessing Severity of Disease in [68Ga]Ga-PSMA-11 PET/CT Study in Prostate Cancer Patients after Radical Prostatectomy.

OBJECTIVE: The objective of this study was to identify the optimal cut-off value of prostate specific antigen (PSA) to assess the extent of the disease in [68Ga]Ga-PSMA-11 PET/CT study in patients after radical prostatectomy. MATERIALS AND METHODS: Retrospective analysis was performed on a group of 215 patients who underwent a [68Ga]Ga-PSMA-11 PET/CT examination because of suspected recurrence after radical prostatectomy. Patients were divided into four groups: 1, no active lesions suggesting recurrence (n = 92); 2, suspected isolated local recurrence (n = 19); 3, oligometastatic disease (n = 82); and 4, polymetastatic disease (n = 22). RESULTS: In group 1, the mean PSA level was 0.962 ng/mL (median: 0.376; min: 0.004; max: 25 ng/mL); in group 2, it was 4.970 ng/mL (median 1.320; min: 0.003; max: 40.350 ng/mL); in group 3, it was 2.802 ng/mL (median: 1.270; min: 0.020; max: 59.670 ng/mL); and in group 4, it was 4.997 ng/mL (median: 3.795; min: 0.007; max 21.110 ng/mL). Statistically significant differences were shown in PSA levels when comparing groups 1 and 2 (p = 0.0025) and groups 3 and 4 (p = 0.0474). The PSA cut-off point for discriminating groups 1 and 2 was 0.831 (sensitivity: 0.684; specificity: 0.772; area under the curve (AUC): 0.775), and for groups 3 and 4, it was 2.51 (sensitivity: 0.682; specificity: 0.780; AUC: 0.720). CONCLUSIONS: Our preliminary data suggested that the PSA level has an essential influence on determining the extent of disease in a [68Ga]Ga-PSMA-11 PET/CT study in patients after radical prostatectomy. Identification of the optimal cut-off values for the oligo- and polymetastatic diseases might be helpful in stratifying these patients.

Problems of diagnostic assessment in advanced pancreatic neuroendocrine neoplasm and treatment implications: a case report and literature review.

We are reporting a case of a 55-year-old woman who was diagnosed as having a non-functioning pancreatic neuroendocrine neoplasm (NF-PNEN), the World Health Organization (WHO) low grade (G1) with liver metastases. In the staging process the positron emission tomography - computed tomography with Fluorine-18-Fluorodeoxyglucose (F-FDG PET-CT) and spiral CT then the gallium-DOTA-octreotate positron emission tomography - computer tomography (68Ga-DOTATATE PET-CT) shown difference in burden of disease. In first line therapy, everolimus (Afinitor®, Novartis Pharma GmbH, Germany) at the oral dose of 10 mg once daily and octreotide long-acting release (Sandostatin LAR®) 30 mg i.m. every 4 weeks were administered. Then, due to disease progression - radioisotope therapy with b-emitter Yttrium-90 (9°Y). Based on this experience and on the review of the literature, we recommend that the discrepancy between the imaging studies could be due to heterogeneity of proliferation rate and somatostatin receptors (SSTR) expression within a primary PNEN and metastases. Therefore in such cases of advanced PNEN WHO G1 in the lack of response to everolimus and octreotide LAR administration isotope therapy without a prior chemotherapy should be considered as a palliative treatment according to ESMO Clinical Practice Guidelines and Polish Network of Neuroendocrine Tumors.

Equilibrium radionuclide ventriculography in the assessment of cardiotoxicity of chemotherapy and chemoradiotherapy in patients with breast cancer.

BACKGROUND: Multidrug chemotherapy increases the efficacy of the treatment, but at the same time rises its cardiotoxicity. The majority of cardiac complications are caused by anthracyclines.Radiation therapy may intensify cardiotoxicity. The aim of this study was to determine early changes of cardiac function using radionuclide ventriculography in patients with breast cancer and to compare the toxicity of AC and AT chemotherapy programs. MATERIAL AND METHODS: The study included 71 patients with breast cancer between the ages of 38 and 71 years. All patients after surgery were qualified for chemotherapy, and for 37 (52%) of them subsequent irradiation treatment was planned.Patients received chemotherapy according to the scheme: AC- 47 patients (66%) and AT - 24 patients (34%). Patients were irradiated using a photon beam (4 to 6 MeV) and an electron beam (6-15 MeV). In all patients, before and six months after the treatment, radionuclide ventriculography was performed. RESULTS: In all 71 patients a reductions in left ventricular ejection fraction (EF) and in peak filling rate (PFR) as well as an increase in the end-systolic and end-diastolic volumes (ESvol,EDvol) were observed. AC chemotherapy, where cumulative anthracycline dose was higher, significantly decreased left ventricular ejection fraction and PFR and increased ESvol. AfterAT chemotherapy the EF reduction proved to be smaller. Radiotherapy did not significantly lower the value of EF as compared to the group of patients who underwent chemotherapy. CONCLUSIONS: Radionuclide ventriculography is a useful method of evaluating the cardiotoxicity of the treatment. Early indicators of myocardial damage are EF, PFR, ESvol and EDvol.AC chemotherapy, where the average cumulative dose of anthracyclines was higher, caused more cardiotoxic effects than AT chemotherapy.Applying additional radiotherapy did not significantly increase the cardiotoxicity of the treatment.

The diagnostic role of 68Ga-DOTATATE PET/CT in the detection of neuroendocrine tumours.

BACKGROUND: Positron emission tomography (PET) combined with computer tomography (CT) using (68)Ga-DOTATATE is a promising method for the evaluation of patients with recognised or suspected neuroendocrine tumours (NET). The aim of this study was to assess the diagnostic value of (68)Ga-DOTATATE PET/CT in the visualisation of the expression of somatostatin receptors (SSTR) and identification of new lesions. MATERIAL AND METHODS: Between December 2009 and January 2011 ninety-seven patients with confirmed (88 cases) or suspected (9 cases) NET underwent (68)Ga DOTATATE PET/CT. The primary, confirmed or suspected, NET localizations were: GEP tumours--71 patients; medullary thyroid carcinoma--4 patients; cancer of an unknown primary--14 patients; and NET in other localisations--8 patients. PET/CT acquisitions were performed using standard techniques, 45 to 60 minutes after the intravenous injection of 111-185 MBq (68)Ga-DOTATATE. RESULTS: (68)Ga-DOTATATE PET/CT detected the presence of lesions demonstrating the somatostatin receptor affinity in 50 of the 97 patients (51.5%) and was negative in 47 patients (48.5%). Among 14 patients with metastatic unknown primary cancer, in 5 patients (45.5%) the primary tumour site was identified, and in 4 patients with medullary thyroid cancer distant metastases with SSTR expression were localized in only one patient. CONCLUSIONS: Our findings confirm the diagnostic role of (68)Ga-DOTATATE PET/CT as an accurate method of identifying primary tumours and distant metastases. It provides information on tumour cell receptors status, which has a significant bearing on planning target radionuclide therapy. Overall, (68)Ga-DOTATATE PET/CT can be used in staging, re-staging, and in regular follow up of oncology patients.

Advances in radionuclide imaging for bone metastases.

Bone scan remains the most frequently requested investigation in any nuclear medicine department. The main reason for this is the exquisite sensivity of the bone scan for lesion detection, combined with clear visualisation of the whole skeleton. The isotope bone scan is now generally accepted as initial investigation of choice in the search for bone metastases from most tumours. 13583 bone scans for metastases were performed in our institution in 1998-2002 years. The frequency of bone metastases was highest in breast, prostate and lung cancer (53,9%, 58,6% and 29,5% respectively). Future progress depends on further advances in specificity of radiotracers and improvements of image acquisition and processing.