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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 20439

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Dr. Anna Mucha-Małecka

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Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow Branch, Garncarska 11, 31-115 Cracow, Poland
Interests: molecular biology; radiobiology; immunotherapy; targeted therapy; radiotherapy; head and neck cancers; HPV infections
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Dear Colleagues,

All over the world, including in Poland, there is ongoing progress in the biology and therapy of malignant neoplasms. In 2017, according to the National Cancer Registry, 164,875 new cases of malignant neoplasms were reported in Poland. Thanks to novel treatment methods, cancer is, in many cases, becoming a chronic condition rather than a fatal disease. Contemporary oncology has a wide arsenal of drugs and therapeutic procedures aimed at eradicating neoplastic cells. Modern cancer treatment is based on the concept of an interdisciplinary and holistic approach to cancer therapy. The development of basic sciences in Poland (radiobiology and molecular biology) allows for the identification and verification of new molecular biomarkers.

Cancer biology research has focused on:

Searching for genetic factors associated with an increased risk of developing malignant neoplasms;
Development of biological prognostic and predictive factors for various types of anticancer treatments;
Identification of new targets for immunotherapy and targeted therapies used in cancer patients;
The significance of microorganisms (e.g., human papillomavirus) in carcinogenesis and the treatment of cancer patients.

Modern oncohematology with bone marrow transplantation, oncological endocrinology, nuclear medicine, oncological and reconstructive surgery, modern radiotherapy and systemic treatments has also developed. Recent reports on breakthrough therapies and ongoing clinical trials grant patients hope to overcome the disease, with personalized cancer therapy based on the molecular profile of tumors currently developing. The introduction of novel therapies in clinics is associated with new side effects; therefore, it is necessary to optimize molecularly targeted treatments and skillfully manage their toxicity. Due to the improvement of treatment results, it is also necessary to remember supportive management, which is an important element of improving the comfort and quality of life of cancer patients.

I invite you to share your results in the field of biology and treatment of malignant neoplasms in your centers in Poland in this Special Issue of Biomedicines.

Dr. Anna Mucha-Małecka
Guest Editor

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Keywords

molecular biology
radiobiology
immunotherapy
targeted therapy
radiotherapy
multimodal therapy

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Published Papers (9 papers)

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9 pages, 923 KiB

Open AccessArticle

Expression Profiles of CDKN2A, MDM2, E2F2 and LTF Genes in Oral Squamous Cell Carcinoma

by Karolina Gołąbek, Grzegorz Rączka, Jadwiga Gaździcka, Katarzyna Miśkiewicz-Orczyk, Natalia Zięba, Łukasz Krakowczyk, Maciej Misiołek and Joanna Katarzyna Strzelczyk

Biomedicines 2022, 10(12), 3011; https://doi.org/10.3390/biomedicines10123011 - 23 Nov 2022

Cited by 6 | Viewed by 1983

Abstract

Background: Oral squamous cell carcinoma (OSCC) is one of the most commonly detected neoplasms worldwide. Not all mechanisms associated with cell cycle disturbances are known in OSCC. Examples of genes involved in the control of the cell cycle are CDKN2A, MDM2, E2F2 and LTF. The aim of this study was to examine the possible association between CDKN2A, MDM2, E2F2 and LTF mRNA expression and influence on clinical variables. Methods: The study group consisted of 88 Polish patients. The gene expression levels were assessed by quantitative reverse transcription PCR. Results: We found no statistically significant differences in the expression level of CDKN2A, MDM2, E2F2 and LTF genes in tumour samples compared to margin samples. No association was found between the gene expression levels and clinical parameters, except E2F2. The patients with G2 tumours had a significantly higher gene expression level of E2F2 than patients with low-grade G1 tumours. Conclusions: We have not demonstrated that a change in expression profiles of genes has a significant impact on the pathogenesis of OSCC. It may also be useful to conduct further studies on the use of E2F2 expression profile changes as a factor to describe the invasiveness and dynamics of OSCC development. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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12 pages, 3112 KiB

Open AccessEditor’s ChoiceArticle

Prognostic Significance of STING Immunoexpression in Relation to HPV16 Infection in Patients with Squamous Cell Carcinomas of Oral Cavity and Oropharynx

by Beata Biesaga, Ryszard Smolarczyk, Anna Mucha-Małecka, Justyna Czapla, Janusz Ryś and Krzysztof Małecki

Biomedicines 2022, 10(10), 2538; https://doi.org/10.3390/biomedicines10102538 - 12 Oct 2022

Cited by 5 | Viewed by 2339

Abstract

Infection with HPV16 in cancers of the oral cavity (OCSCC) and oropharynx (OPSCC) is, today, an important etiological and prognostic factor. Patients with HPV-positive OPSCC have a better prognosis than uninfected patients. However, in over 40% of these patients, cancer progression is noticed. Their identification is particularly important due to the ongoing clinical trials regarding the possibility of de-escalation of anticancer treatment in patients with HPV-positive OPSCC. Some studies suggest that there is possibility to differentiate prognosis of HPV16-positive patients by STING (Stimulator of Interferon Genes) immunoexpression. The aim of the present study was to analyze the influence of STING immunoexpression on overall (OS) and disease-free survival (DFS) of patients with HPV16-positive and -negative OCSCC and OPSCC. The study was performed in a group of 87 patients with OCSCC and OPSCC for which in our earlier study active HPV16 infection was assessed by P16 expression followed by HPV DNA detection. To analyze STING immunoexpression in tumor area (THS) and in adjacent stromal tissues (SHS) H score (HS) was applied. In the subgroup with HPV16, active infection patients with tumors with THS had significantly better DFS (p = 0.047) than those without THS. In this subgroup, TSH did not significantly influence OS, and SHS did not significantly correlate with OS and DFS. In the subgroup of patients without active HPV16 infection, THS and SHS also did not significantly influence patients’ survival. Presented results indicated prognostic potential of tumor STING immunoexpression in patients with active HPV16 infection in cancers of oral cavity and oropharynx. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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14 pages, 1367 KiB

Open AccessArticle

Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience

by Renata Pacholczak-Madej, Aleksandra Grela-Wojewoda, Mirosława Puskulluoglu, Joanna Lompart, Manuela Las-Jankowska, Katarzyna Krawczak, Ewa Wrona, Lech Zaręba, Justyna Żubrowska, Jerzy Walocha, Stanisława Bazan-Socha and Marek Ziobro

Biomedicines 2022, 10(10), 2528; https://doi.org/10.3390/biomedicines10102528 - 10 Oct 2022

Cited by 2 | Viewed by 2169

Abstract

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07–0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09–0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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11 pages, 923 KiB

Open AccessArticle

Pre-Treatment Hemoglobin Concentration and Absolute Monocyte Count as Independent Prognostic Factors for Survival in Localized or Locally Advanced Prostate Cancer Patients Undergoing Radiotherapy

by Łukasz Magrowski, Oliwia Masri, Jakub Ciepał, Gabriela Depowska, Zuzanna Nowicka, Rafał Stando, Krystyna Chimiak, Gabriela Bylica, Barbara Czapla, Małgorzata Masri, Franciszek Cichur, Iwona Jabłońska, Marta Gmerek, Piotr Wojcieszek, Tomasz Krzysztofiak, Jacek Sadowski, Rafał Suwiński, Paweł Rajwa, Matthias Moll, Gregor Goldner, Wojciech Majewski and Marcin Miszczyk Show full author list Hide full author list

Biomedicines 2022, 10(10), 2514; https://doi.org/10.3390/biomedicines10102514 - 8 Oct 2022

Cited by 3 | Viewed by 2025

Abstract

The prognostic value of inflammatory indices, such as the absolute monocyte count (AMC), has been a subject of interest in recent prostate cancer (PCa) studies, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized diseases. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival and was based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data were available for all cases and were based on the National Cancer Registry, with a median observation time of 120 months (Interquartile Range (IQR) 80.9–144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox Proportional Hazards Regression model was used for analysis. The median age was 68.8 years (IQR 63.3–73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0–19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, Gleason Grade Group, clinical T stage and maximum prostate-specific antigen concentration. This study demonstrates that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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14 pages, 1600 KiB

Open AccessArticle

MGMT Promoter Methylation as a Prognostic Factor in Primary Glioblastoma: A Single-Institution Observational Study

by Mateusz Szylberg, Paweł Sokal, Paulina Śledzińska, Marek Bebyn, Stanisław Krajewski, Łukasz Szylberg, Aneta Szylberg, Tadeusz Szylberg, Kamil Krystkiewicz, Marcin Birski, Marek Harat, Robert Włodarski and Jacek Furtak

Biomedicines 2022, 10(8), 2030; https://doi.org/10.3390/biomedicines10082030 - 20 Aug 2022

Cited by 23 | Viewed by 3703

Abstract

Glioblastoma is the most malignant central nervous system tumor, which represents 50% of all glial tumors. The understanding of glioma genesis, prognostic evaluation, and treatment planning has been significantly enhanced by the discovery of molecular genetic biomarkers. This study aimed to evaluate survival in patients with primary glioblastoma concerning O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation and other clinical factors. The study included 41 newly diagnosed glioblastoma patients treated from 2011 to 2014 in the 10th Military Research Hospital and Polyclinic, Poland. All patients underwent surgical resection followed by radiation and chemotherapy with alkylating agents. The MGMT promoter methylation was evaluated in all patients, and 43% were found to be methylated. In 26 and 15 cases, gross total resection and subtotal resection were conducted, respectively. Patients with a methylated MGMT promoter had a median survival of 504 days, while those without methylation had a median survival of 329 days. The group that was examined had a median age of 53. In a patient group younger than 53 years, those with methylation had significantly longer overall survival (639 days), compared to 433.5 days for patients without methylation. The most prolonged survival (551 days) was in patients with MGMT promoter methylation after gross total resection. The value of MGMT promoter methylation as a predictive biomarker is widely acknowledged. However, its prognostic significance remains unclear. Our findings proved that MGMT promoter methylation is also an essential positive prognostic biomarker. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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13 pages, 1458 KiB

Open AccessArticle

A New Approach to Imaging and Rapid Microbiome Identification for Prostate Cancer Patients Undergoing Radiotherapy

by Ewelina Maślak, Wioletta Miśta, Michał Złoch, Dominika Błońska, Paweł Pomastowski, Fernanda Monedeiro, Bogusław Buszewski, Jolanta Mrochem-Kwarciak, Katarzyna Bojarska and Dorota Gabryś

Biomedicines 2022, 10(8), 1806; https://doi.org/10.3390/biomedicines10081806 - 27 Jul 2022

Cited by 7 | Viewed by 2101

Abstract

(1) Background: Little is known about the impact of urinary microflora, in particular, its effects on side effects after radiotherapy. The use of mass spectrometry identification method (MALDI) may bring a new look at the issue of the composition and significance of the urinary microbiome. This study aimed to use the mass spectrometry identification method (MALDI) to identify the microbiome of urine samples collected from 50 irradiated prostate cancer patients. (2) Methods: Blood and urine samples were collected before gold marker implantation, at the start and last day of radiotherapy, 1, 4 months after. Patients do not always collect the urine from the midstream; therefore, samples were collected from the first void and midstream in 12 patients for MALDI analysis; in the remaining 38 patients—from the midstream void for MALDI and biochemical analysis. (3) Results: Microorganisms were present in 140/181 urine samples. We found 33 different species 3G(−) and 30G(+). The most frequently isolated strains were: Staphylococcus haemolyticus, Staphylococcus epidermidis, Staphylococcus hominis, Enterococcus faecalis, and Micrococcus luteus. When comparing the type of urine samples, bacteria were more common in samples from the first-void urine than from the midstream one. The absence of bacteria was found in 12.2% of samples from the first-void urine and in 24.7% from the midstream. There was no difference in the total incidence of species between streams (p = 0.85). Before fiducial implantation, the total number of detected bacterial species was significantly higher in comparison to the end of radiotherapy (p = 0.038), indicating that the administered therapy resulted in depleting the local microbiome. One month after radiotherapy, an increase in the number of isolated bacteria was observed. The number of bacterial species in urine did not correlate with blood parameters. The presence of leukocytes (p = 0.013) and proteins (p = 0.004) in urine was related to a greater variety of bacteria found in urine specimens. (4) Conclusions: We obtained a similar spectrum of bacteria from the initial and middle urine streams. We also showed that there is a change in bacteria species affected by the treatment of prostate cancer patients, with both antibiotics before gold fiducial implantation and radiotherapy. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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11 pages, 952 KiB

Open AccessArticle

The Role of Salvage in the Management of Patients with Sinonasal Squamous Cell Carcinoma

by Urszula Kacorzyk and Tomasz Wojciech Rutkowski

Biomedicines 2022, 10(6), 1266; https://doi.org/10.3390/biomedicines10061266 - 28 May 2022

Cited by 2 | Viewed by 1791

Abstract

Objectives: This paper presents and discusses the rate and outcome of salvage according to various factors for patients with sinonasal squamous cell carcinoma (SNSCC). Methods: Data of 79 patients treated radically due to SNSCC between 2000 and 2016 in the National Cancer Research Institute, Gliwice branch, were analyzed. Surgery was the primary treatment in 63 (79%) of patients. The ratio, type, and effectiveness of salvage was assessed and correlated with prognostic factors. Probabilities of overall survival (OS), local control (LC), nodal control (NC), and locoregional control (LRC) were assessed and compared between the groups. Results: The 5-year LC, NC, and LRC survival rates were 62%, 75%, and 53%, respectively. The 5-year OS rate was 51%. In 34 (43%) patients, treatment failure was reported, and salvage was performed in 17 (50%) of them. It was shown that patients after any salvage had significantly longer 2- and 3-year OS rates when compared to patients with no salvage: 52% vs. 7% and 38% vs. 0%, respectively (p = 0.004). Two- and three-year OS rates for patients after effective and ineffective salvage were 83% vs. 33% and 83% vs. 11%, respectively (p = 0.02). For patients with effective salvage, OS did not differ significantly when compared to the OS of primarily cured patients (p = 0.6). Conclusions: For SNSCC patients after treatment failure, salvage is possible in half of the cases and can improve their overall survival even if not finally successful. Moreover, effective salvage can compensate for the failure and give the same ultimate OS as in primarily cured patients. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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Review

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11 pages, 268 KiB

Open AccessReview

Shifting Treatment Paradigms: Improvements in HR-Positive, HER-2- Negative Breast Cancer Care in Poland from a Clinical Perspective

by Marek Ziobro and Aleksandra Grela-Wojewoda

Biomedicines 2023, 11(2), 510; https://doi.org/10.3390/biomedicines11020510 - 10 Feb 2023

Viewed by 1728

Abstract

Patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer constitute about 70% of the breast cancer population. About 35% of these patients develop distant metastases and their treatment will be palliative. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors were shown to significantly improve the outcomes of these patients. In combination with endocrine therapy, they have become the standard first-line treatment for HR-positive, HER2-negative breast cancer. In Poland, treatment with CDK4/6 inhibitors is reimbursed only for patients participating in the drug program of the Ministry of Health. However, fulfilling the eligibility criteria for the program may be challenging both for patients and for clinicians. This may lead to a delay in treatment with CDK4/6 inhibitors or a decision to use older and less effective drugs that are more widely available. The aim of this review was to compare the efficacy of first-line therapies in patients with HR-positive, HER2-negative metastatic breast cancer depending on the use of CDK4/6 inhibitors. We compared the efficacy of previous standard therapies with that of ribociclib, a CDK4/6 inhibitor, based on the median progression-free survival (PFS) as an outcome. Median PFS is not affected by the efficacy of subsequent treatment lines and is easy to interpret both for clinicians and for patients. The first-line treatment with chemotherapy or endocrine therapy (without CDK4/6 inhibitors) prolongs median PFS by several months and even to over a dozen months. The first-line treatment with endocrine therapy plus CDK4/6 inhibitors provides an opportunity to achieve a median PFS of more than 25 months and to prolong it by about 9 to 14 months. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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12 pages, 265 KiB

Open AccessStudy Protocol

Escalating a Biological Dose of Radiation in the Target Volume Applying Stereotactic Radiosurgery in Patients with Head and Neck Region Tumours

by Paweł Polanowski, Krzysztof Składowski, Dorota Księżniak-Baran, Aleksandra Grządziel, Natalia Amrogowicz, Jolanta Mrochem-Kwarciak, Agnieszka Pietruszka, Marek Kentnowski and Katarzyna Polanowska

Biomedicines 2022, 10(7), 1484; https://doi.org/10.3390/biomedicines10071484 - 23 Jun 2022

Viewed by 1545

Abstract

Background: The treatment of head and neck tumours is a complicated process usually involving surgery, radiation therapy, and systemic treatment. Despite the multidisciplinary approach, treatment outcomes are still unsatisfactory, especially considering malignant tumours such as squamous cell carcinoma or sarcoma, where the frequency of recurrence has reached 50% of cases. The implementation of modern and precise methods of radiotherapy, such as a radiosurgery boost, may allow for the escalation of the biologically effective dose in the gross tumour volume and improve the results of treatment. Methods: The administration of a stereotactic radiotherapy boost can be done in two ways: an upfront boost followed by conventional radio(chemo)therapy or a direct boost after conventional radio(chemo)therapy. The boost dose depends on the primary or nodal tumour volume and localization regarding the organs at risk. It falls within the range of 10–18 Gy. Discussion: The collection of detailed data on the response of the disease to the radiosurgery boost combined with conventional radiotherapy as well as an assessment of early and late toxicities will contribute crucial information to the prospective modification of fractionated radiotherapy. In the case of beneficial findings, the stereotactic radiosurgery boost in the course of radio(chemo)therapy in patients with head and neck tumours will be able to replace traditional techniques of radiation, and radical schemes of treatment will be possible for future development. Full article

(This article belongs to the Special Issue State-of-the-Art Cancer Biology and Therapeutics in Poland)

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