Cancer care for Ukrainian refugees during the first 6 weeks of 2022 Russian invasion - An experience of a cancer reference centre in Poland.

BACKGROUND: On 24th of February 2022, Ukrainian cancer patients had to face a new war. Here we describe an experience of the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow in providing cancer care for Ukrainian refugees during the initial 6 weeks of war. We present patients' characteristic, point out the main challenges and share initiatives undertaken. MATERIALS AND METHODS: For this cross-sectional analysis, we have gathered demographic and clinical data together with date of crossing the Polish-Ukrainian border for 112 Ukrainian refugees with cancer who had their first-time oncology consultation between 24th February and 8th April 2022. We have also implemented national guidelines and created local procedures, interventions and policies to manage this situation. RESULTS: The peak of patient inflow was the third week of War and refugees accounted for 13% of all first-time patients within that period of time. The majority of refugees were women (86%), treated radically (57%) with breast cancer (43%). Most of the patients required systemic treatment (67%). Amongst the main challenges at the time were differences in the reimbursement system, communication issues, lack of patients' documentation or tissue samples, prolonged diagnostic or treatment interruptions, increased risk of COVID-19 infections, chemotherapy side effects, and lack of procedures. Legal, procedural and organizational steps implemented at the local and national level were described. CONCLUSIONS: The Russian invasion on Ukraine forced an unexpectedly high number of Ukrainian cancer patients to seek help abroad, leading to the straining of the health care system in Poland.

Biomarkers of Trastuzumab-Induced Cardiac Toxicity in HER2- Positive Breast Cancer Patient Population.

Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

Long-Term Outcomes of Targeted Therapy after First-Line Immunotherapy in BRAF-Mutated Advanced Cutaneous Melanoma Patients-Real-World Evidence.

BACKGROUND: Currently, limited data on targeted therapy and immunotherapy sequencing in patients with BRAF-mutant melanoma is available. Targeted therapy and immunotherapy are expected to be comparable in terms of overall survival (OS) when used as second-line therapies; therefore, understanding the characteristics of patients who completed sequential treatment is needed. METHODS: The primary objective of this study was to analyze the efficacy of BRAFi/MEKi activity as second-line therapy in patients with advanced melanoma. We also aimed to describe the clinical characteristics of patients with advanced melanoma who were treated sequentially with immunotherapy and targeted therapy. We enrolled 97 patients treated between 1st December 2015 and 31st December 2020 with first-line immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors; and for the second-line treatment with at least one cycle of BRAFi/MEKi therapy with follow-up through 31 January 2022. RESULTS: Median OS since first-line treatment initiation was 19.9 months and 12.8 months since initiation of BRAFi/MEKi treatment. All BRAFi/MRKi combinations were similarly effective. Median progression free survival (PFS) was 7.5 months since initiation of any BRAFi/MEKi treatment. CONCLUSIONS: BRAFi/MEKi therapy is effective in the second-line in advanced and metastatic melanoma patients. For the first time, the efficacy of all BRAFi/MEKi combinations as second-line therapy is shown.

Adjuvant combined therapy with trastuzumab in patients with HER2­ positive breast cancer and cardiac alterations: implications for optimal cardio­oncology care.

INTRODUCTION: Recently, the prognosis of patients with HER2­positive breast cancer (BC) has improved significantly owing to the use of combined treatment modalities. However, systemic treatment is as-sociated with increased risk of cardiotoxicity. OBJECTIVES: We aimed to assess subclinical cardiac alterations during the final stage of adjuvant com-bined therapy, that is, trastuzumab therapy (TT), as potential predictors of late cardiac complications in patients with HER2­positive BC. PATIENTS AND METHODS: We enrolled 251 patients with HER2­positive BC treated with a radical local therapy, adjuvant chemotherapy (anthracyclines or anthracyclines + taxanes), and immunotherapy (trastuzumab). Patients underwent 6 echocardiographic examinations: at baseline, during TT, and after TT, with assessment of left ventricular ejection fraction (LVEF), degree of valvular regurgitation, and cardiac chamber diameters. RESULTS: Valvular fibrosis (28.4% of patients) was associated with older age, hypertension at baseline, and a higher degree of regurgitation during TT. Reduced LVEF, greater regurgitation, and larger cardiac chamber diameters were noted during TT. The patients who received higher anthracycline doses showed a greater degree of aortic insufficiency and a larger right ventricular diameter. Reduced LVEF during TT was associated with radiotherapy or chemotherapy and the degree of valvular regurgitation. Significantly larger diameters were observed in older patients and in those with comorbidities at baseline, high body mass index, and regurgitation. CONCLUSIONS: Asymptomatic subclinical cardiac alterations during TT may predict late cardiac complica-tions; however, longer follow­up is necessary to confirm this hypothesis. Patients with HER2­positive BC should be closely monitored for possible cardiac alterations during and after therapy to ensure optimal care and guide therapeutic decision­making.

Development of immunity-related adverse events correlates with baseline clinical factors, survival and response to anti-PD-1 treatment in patients with inoperable or metastatic melanoma.

BACKGROUND: The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory. MATERIAL AND METHODS: Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study. RESULTS: Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093). CONCLUSION: The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.

Anti-programmed cell death-1 therapy in octogenarian and nonagenarian advanced/metastatic melanoma patients.

Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three patients were aged 80-100, 218 patients were aged 65-79, and 208 patients were <65 years old. Baseline parameters were comparable. The median overall survival (OS) was 14.7, 18.7, 25.9, and the median progression-free survival (PFS) was 8.7, 7.7, and 6.2 months in the age groups of 80-100, 65-79, and <65 years, respectively. The median melanoma-specific survival (MSS) was 22.5, 27.8, and 31.6 months in the age groups of 80-100, 65-79, and <65 years, respectively. There was no statistically significant difference in OS (P = 0.2897), PFS (P = 0.7155), and MSS (P = 0.9235) between the group of 80-100 years old vs. 65-79 and vs. <65 years old patients. Overall response rate and disease control rate was similar in all groups (P = 0.06974 and P = 0.89435, respectively). Overall, the immune-related adverse event (irAE) rate was comparable in the three age groups (41, 34, and 37.5% in the groups of patients aged 80-100, 65-79, and <65 years, respectively). Also, the rates of G3 and G4 irAEs were comparable (4, 6, and 7% in the groups of patients, respectively). The efficacy and toxicity of anti-PD-1 therapy in octogenarians and nonagenarians with metastatic melanoma are similar as in patients aged <65 years and 65-79 years. The patients' age should not be considered as an exclusion criterion for anti-PD-1 treatment.

Real-world treatment practice in patients with advanced melanoma.

INTRODUCTION: The treatment outcomes of patients with advanced/metastatic melanoma were poor before the use of new therapeutic options. MATERIAL AND METHODS: A retrospective analysis was conducted among 287 patients with unresectable stage III and stage IV melanoma treated at the Maria Sklodowska-Curie National Research Institute of Oncology Cracow Branch, from 2013 to 2019. All enrolled patients were treated with immunotherapy (IT; consisting of pembrolizumab/nivolumab, or ipilimumab) or target therapy (TT; consisting of vemurafenib ±cobimetinib or dabrafenib ±trametinib) in at least one treatment line. RESULTS: mutation was detected in 152 (55%) patients. In general, the majority of patients (92%) were in very good or good condition (Eastern Cooperative Oncology Group [ECOG] 0 or 1). Brain metastasis was detected in 64 (22%) patients. Median OS and PFS in the experimental group from the beginning of the first-line treatment were 14.9 and 6.7 months, respectively. Across the study population, as a first-line treatment patients received IT, TT as well as CHT, and the median OS was 19.2, 12.6 and 15.9 months, respectively. Multivariate analysis confirmed that normal LDH levels, no brain metastases, ECOG 0, and objective response to the treatment were strong predictors of longer OS. For PFS, absence of brain metastases, ECOG 0, and treatment response were found to be predictive factors on multivariate analysis. CONCLUSIONS: The administration of new therapies for the treatment of patients with advanced/disseminated melanoma significantly prolonged survival in this group of patients. Nevertheless, further studies should be conducted to assess the effectiveness of various sequences of treatment.

Immune checkpoint inhibitors therapy in older patients (≥ 70 years) with metastatic melanoma: a multicentre study.

INTRODUCTION: The use of immunotherapy in older patients remains challenging due to very few data on the efficacy and safety of treatment in this group. AIM: To analyse the efficacy and safety of immunotherapy with checkpoint inhibitors in older patients (≥ 70 years) with metastatic melanoma. MATERIAL AND METHODS: In the Maria Sklodowska-Curie Institute - Oncology Centre, between 2011 and 2017, 318 non-resectable or metastatic melanoma patients were treated with immune checkpoint inhibitors: anti-CTLA-4 or/and anti-PD-1. Eighty-two patients were ≥ 70 years (median age: 76 years; range: 70-90 years). Among this group 10% of patients had brain metastases, 24% of patients had BRAF mutant melanoma, and co-morbidities were present in 86% of patients (mainly hypertension, cardiovascular diseases and/or diabetes). RESULTS: Median PFS and OS were similar in patients < 70 years and ≥ 70 years. In the group of patients ≥ 70 years old, the 2-year OS rate (from the start of immunotherapy) was 27%, and in patients aged < 70 it was 28% (p = NS). Two-year progression-free survival was 13.7% in the group of patients ≥ 70 years old and in patients aged < 70 it was 13% (p = NS). Patients ≥ 70 years of age were significantly less likely to have a BRAF mutation (p = 0.020). The presence of co-morbidities was not associated with an increased risk of immunotherapy (p = 0.790). CONCLUSIONS: The survival and toxicity profile in the older patients treated with immune checkpoint inhibitors are similar to younger patients. Therefore, the age as a clinical factor should not exclude this population from the most effective therapy used nowadays in melanoma treatment.

FOLFOX4 with cetuximab vs. UFOX with cetuximab as first-line therapy in metastatic colorectal cancer: The randomized phase II FUTURE study.

INTRODUCTION: The purpose of this study was to assess the efficacy and safety of FOLFOX4, comprising infusional 5-fluorouracil (5-FU)/leucovorin (LV) and oxaliplatin, with cetuximab compared with UFOX, comprising UFT, an oral prodrug of 5-FU, LV, and oxaliplatin, with cetuximab as first-line treatment for mCRC. PATIENTS AND METHODS: Patients, unselected by tumor KRAS status, were randomized 1:1 to FOLFOX4 with cetuximab or UFOX with cetuximab. Treatment was continued until disease progression or unacceptable toxicity. The primary end point, assessed in the intention-to-treat population, was progression-free survival (PFS). Secondary end points included tumor response, overall survival, and safety. Outcome according to KRAS mutation status was investigated. RESULTS: Recruitment was curtailed at 302 patients after reporting of the importance of tumor KRAS mutation status for cetuximab activity. Baseline characteristics were balanced between treatment groups. PFS was significantly longer in the FOLFOX4 with cetuximab group compared with UFOX with cetuximab group (median 8.2 vs. 6.6 months; hazard ratio, 0.68; 95% confidence interval [CI], 0.52-0.89; P = .0048). The response rate was also significantly greater in the FOLFOX4 with cetuximab group (51.3% vs. 37.5%, respectively; odds ratio, 1.76; 95% CI, 1.11-2.78; P = .0160), although overall survival was comparable. In the KRAS wild type subgroup, efficacy outcomes were similar to those in the intention-to-treat population. Side effect profiles were manageable and consistent with expectations. CONCLUSION: In the first-line treatment of mCRC, UFOX with cetuximab had an acceptable safety profile but inferior activity compared with FOLFOX4 with cetuximab in relation to PFS and response. The regimens were comparable with regard to overall survival.

Diagnostic, predictive and prognostic verification of DNA flow cytometric measurements performed at diagnosis for non-Hodgkin's lymphoma adult patients.

More than ten years ago we made first attempts at valuating a prognostic power of flow cytometric DNA measurement results for patients with non-Hodgkin's lymphoma. In multivariate overall survival analysis, S-phase fraction (SPF) showed to be the only independent prognostic factor within the group of patients with low grade lymphomas. In this paper, we have tried to check our previous results in a greater group of patients with longer follow-up, within the specific types of B-cell and T/NK-cell lymphomas verified and classified according to criteria of the WHO 2008 classification. The study was performed on the material obtained from biopsies (85% of lymph nodes) of 484 NHL patients. Patients were diagnosed from 1991 to 2007. The medium follow-up time for living patients was 69 months (range: 25-202 months). All specimens were verified histologically and immunohistochemically. Ploidy and SPF were determined by flow cytometry on fresh tissue obtained during the diagnostic procedure. The diagnostic importance of ploidy and SPF has been confirmed. Ploidy had no predictive or prognostic impact in any of the NHL types, whereas SPF was found to be an independent predictive or prognostic factor in B-CLL/SLL, DLBCL and ALCL.

[Chemotherapy of advanced non small cell lung cancer: effect on survival and symptoms affecting quality of life]. / Ocena wplywu chemioterapii na czas przezycia i wybrane objawywplywajace na jakosc zycia chorych na niedrobnokomórkowegoraka pluca w IIIB i IV stopniu zaawansowania.

INTRODUCTION: The study presents treatment results of 168 patients with non small cell lung cancer in stage IIIB and IV treated since year 2002 to 2006 in Oncological Center in Cracow. MATERIAL AND METHODS: Four regimens of chemotherapy: EP (cisplatin, vepesid), MVP (mitomycin C, vinblastin, cisplatin), PN (cisplatin,vinorelbin) and PG (cisplatin, gemcytabin) were used. RESULTS: Average survival time in group treated with MVP regimen was 7,8 months (median 4,3 months), PG 7,1 months (median 7,3 months), EP 10,2 months (median 7,5 months), PN 14,1 months (median 9,8 months). Differences in median survival time were not significant. Average time to progression in group treated with MVP regimen was 3,5 months (median 2,6 months), PG 5,2 months (median 5,8 months): EP 6,6 months (median 5,2 months), PN 6,7 months (median 5,6 months). Improvement in control of symptoms regarding dyspnea, pain and cough was reached in 60%, 38,7% and 60% of patients respectively. There were no significant differences between chemotherapy regimens regarding improvement in symptoms control. CONCLUSIONS: Cisplatin + vinorelbin regimen can be recommended as standard method because of the best treatment results.