Wspolczesna Onkologia-Contemporary Oncology最新文献

Introduction: The study aimed to determine the immunoexpression levels of polymerase delta 1 catalytic subunit (POLD1), a catalytic and proofreading subunit of DNA polymerase delta, in the sections of colorectal cancer (CRC), and to evaluate the significance of POLD1 as a potential prognostic factor in CRC.

Material and methods: Paired, tumour and non-cancerous tissue samples of the large intestine distant to the neoplasm were collected from the postoperative material of 78 patients who underwent surgical resection of CRC tumours. Polymerase delta 1 catalytic subunit protein levels were determined using immunohistochemistry. Clinical, pathomorphological, and survival data of the patients were pooled. In addition, POLD1 mRNA expression levels of 599 CRC patients were extracted from The Cancer Genome Atlas (TCGA) datasets and subjected to statistical and survival analysis including the Kaplan-Meier method followed by the log-rank test.

Results: Immunoexpression of POLD1 was found in the nuclei of the tumour cells and epithelial cells of unchanged intestinal mucosa. Polymerase delta 1 catalytic subunit immunoreactivity in the tumour was heterogenous, and the average immunoreactivity score was decreased in cancer cells when compared to the mucosa of matched sections of unchanged large intestine (p = 0.0259). However, POLD1 expression at the protein and mRNA levels did not associate with clinicopathological characteristics of the patients and their survival.

Conclusions: Despite previous studies suggesting that POLD1 genetic alterations could be promising molecular biomarkers in CRC, our results do not support any prognostic significance of POLD1 expression in CRC.

Colorectal cancer (CRC) is the third most common cancer; it is one of the leading malignancies contributing to cancer mortality. Colorectal cancer is the third most diagnosed cancer in men and the second in women worldwide. Diagnosis of CRC depends on several clinical features such as age, primary site, tumor-node-metastasis stage, genetic parameters and the presence or absence of metastasis. The latter is a phenomenon that is induced by the shedding of tumor cells in the blood circulation by the primary tumor. Such cells are known as circulating tumor cells (CTCs). The detection of CTCs is quite challenging due to their scarceness; thus it requires their enrichment and characterization. Studying the utility of CTCs in the diagnosis of CRC has been the aim of several studies; they demonstrated that ≥ 3 CTCs in 7.5 ml of blood is correlated with a worse prognosis and short progression-free and overall survival. Circulating tumor cells have also been monitored to study treatment response and predict future relapses. The present review aims to bring to light the different techniques used to detect and characterize these malignant cells in the peripheral blood of cancer patients as well as the clinical relevance of CTCs in CRC patients.

Introduction: The mechanistic target of rapamycin (mTOR) coordinates the growth and metabolism of eukaryotic cells with a central role in the regulation of many fundamental cellular processes. It is strongly connected to phosphatidylinositol 3-kinase (PI3K) and AKT signaling. Activation of the PI3K/AKT/mTOR pathway leads to a profound disruption in the control of cell growth and survival, which ultimately leads to competitive growth advantage, metastatic competence, angiogenesis and therapeutic resistance.

Material and methods: To explore the common competitive adenosine triphosphate (ATP) inhibitors PI3K/AKT and PI3K/mTOR, we built a 2D mTOR-SAR model that predicted the bioactivity of AKT and PI3K inhibitors towards mTOR. The interaction of the best inhibitors was evaluated by docking analysis and compared to that of the standard AZ8055 and XL388 inhibitors.

Results: A mechanistic target of rapamycin-quantitative structure-activity relationship (mTOR-QSAR) model with a correlation coefficient (R²) of 0.80813 and a root mean square error of 0.17756 was obtained, validated and evaluated by a cross-validation leave-one-out method. The best predicted AKT and PI3K inhibitor pIC50 activities were 9.36-9.95 and 9.23-9.87 respectively.

Conclusions: After docking and several comparisons, the inhibitors with better predictions showed better affinity and interaction with mTOR compared to AZ8055 and XL388, so we have found that 2 AKT inhibitors and 9 mTOR inhibitors met the Lipinski and Veber criteria and could be future drugs.

Introduction: The primary approach for managing skin cancer involves surgery, although radical radiotherapy (RT) may be considered as an alternative option in cases where patients decline the treatment themselves or are not eligible for surgical intervention. Herein we assess single-institution material in terms of the use of hypofractionated QUAD SHOT RT in patients disqualified from surgery.

Material and methods: Between December 2019 and December 2022, nine patients with locally advanced non-melanoma skin cancer were disqualified from surgery and as a result were treated at the Radom Oncology Centre, Poland. Patients were treated with the Radiation Therapy Oncology Group 8502 QUAD SHOT regimen (14.8 Gy/4 fractions, twice-daily treatment with a 6 h interval, on 2 consecutive days). Courses were repeated every 4 weeks 3 times using volumetric modulated arc therapy (VMAT).

Results: Grade 2 toxicities were observed in 4 of 9 (44.4%) patients, no grade ≥ 3 acute toxicity was observed. The median age was 79.1 (60-98) years. Irradiated areas were as follows: nose skin (2), cheek (2), eyebrow with eyelid (1), forehead (1), temple (1), sternum (1), and scapula (1). Performance status was as follows: WHO II - 5 patients (55.6%), WHO I - 3 patients, WHO III - one patient. One patient underwent 3 RT courses in 2 areas for a total of 6 treatment courses, 6 patients received 3 courses of treatment, and 2 patients received 2 courses. Additionally, as of 14 March 2023, four patients died of non-malignant causes.

Conclusions: QUAD SHOT schedule with VMAT RT may be an effective palliative treatment method with a good response rate, which positively affects patients' quality of life in locally advanced non-melanoma skin cancer patients disqualified from surgery.

Introduction: The geriatric nutritional risk index (GNRI) is an index of nutritional status associated with clinical outcomes in various cancers; however, its prognostic value in biliary tract cancer (BTC) remains to be elucidated. This retrospective study aimed to investigate the association between preoperative GNRI and long-term prognosis of patients with BTC undergoing surgical resection.

Material and methods: A total of 213 patients were included. The relationships between GNRI and clinicopathological variables, including inflammatory markers such as C-reactive protein (CRP) and neutrophil-to-lympho-cyte ratio, were analysed. The impact of GNRI on overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier curves and Cox proportional hazards models.

Results: Applying a GNRI cut-off of 98, the low-GNRI group comprised 135 patients (63%). The low-GNRI group had elevated carbohydrate antigen 19-9 and CRP levels, high rates of preoperative biliary stenting, lymph node metastases, and perineural invasion, and a lower rate of R0 resection than the high-GNRI group. Both OS and RFS in the low-GNRI group were significantly lower. In multivariate analysis, low GNRI was a significant predictor of poor OS (hazard ratio [HR], 1.731; 95% CI: 1.111-2.696; p = 0.015) and RFS (HR, 1.900; 95% CI: 1.231-2.931; p = 0.004), independently of inflammatory and tumour markers, as well as of pathological features.

Conclusions: Preoperative GNRI may be an easily accessible predictor of poor prognosis in patients with BTC undergoing surgical resection.

Introduction: This paper presents the role of attachment style in determining an individual's way of coping with stress, which in turn helps to understand the differences in response and adjustment to cancer among cancer patients. Cancer is an illness that causes overwhelming distress, and dealing with it requires social support, among other coping strategies.

Material and methods: Studies show that social support is associated with a decrease in psychological symptoms and a better quality of life in cancer patients. According to attachment theory, one's perception of threat, way of signaling distress, and strategies of coping with it, with special consideration for the ability to use a partner's support, relies on differences in avoidance and anxiety (attachment style dimensions).

Results: People with high avoidance (associated with deactivating attachment strategy) tend not to seek support from others and rely on themselves.

Conclusions: People with high anxiety (associated with deactivating attachment strategy) tend to display strong emotional responses, permanently seek attention and support from others, and yet are less able to feel comforted by them.

Introduction: Salivary gland tumours are rare neoplasms. Pleomorphic adenoma (PA) is the most frequent benign lesion. Myoepithelial carcinoma (MECA) is rarely recognized malignancy, but the prognosis is unfavourable. The aim of this study was to identify genetic rearrangements that might be responsible for dynamic MECA progression in patients with primary radical PA excision.

Material and methods: Next-generation sequencing (NGS) of 1500 gene coding sequences was performed in primary and recurrent tumour tissue collected from 2 patients, in whom PA was initially diagnosed and within one year multifocal MECA was detected. Formalin-fixed paraffin-embedded blocks with tumour tissues were subject to NGS analysis, involving small-scale mutations, as well as focal and chromosomal arm-level copy number changes.

Results: This study showed mutations in the FGFR2 gene in PA and MECA tissues, obtained from both patients. One of them, pathogenic mutation p.Pro253Arg, was associated with sensitivity to registered drug inhibitors. Additionally, FGFR1, EGFR, and CDK4/CDK6 amplification, as well as CDKN2A/B deletion, were detected in one case. Furthermore, mutations in suppressor gene APC2 and PIK3C2A were detected, but only in MECA tissue. The analysis also identified the following chromosomal copy alterations: 4q12-q13.3, 9p21.3, 5q23.1-q34, del8p23.3-p12, and del13q21.31-q31.1.

Conclusions: Rearrangement of the FGFR2 gene, identified in primary PA and MECA ex PA samples of both our patients, may be responsible for the malignant transformation and the disease progression. Further studies are encouraged to confirm the relevance of the findings. The therapy option with FGFR2 inhibitors may be considered in advanced or metastatic MECA ex PA with confirmed FGFR2 mutations.

Introduction: Geriatric patients with metastatic renal cell carcinoma (mRCC) are underrepresented in clinical trials. Evaluation of the efficacy of the treatment and assignation of individuals to proper prognostic groups is an absolute necessity to guarantee them the best possible care.

Material and methods: A total of 138 geriatric patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) at the Maria Skłodowska-Curie National Research Institute of Oncology were retrospectively analyzed to determine whether the body mass index (BMI) and pan-immune-inflammation value (PIV) are prognostic values for overall survival (OS) and progression-free survival (PFS) in this type of cancer. For this purpose, Cox's proportional hazard model was used.

Results: The median duration of follow-up for surviving patients was 46.6 (95% CI: 17.4-75.8) months. The median OS and PFS were respectively 33.8 months (95% CI: 23.8-47.8) and 19.1 months (95% CI: 15.0-23.3). BMI (p = 0.034) and PIV (p < 0.001) were statistically significantly associated with OS, and PIV (p = 0.001) was statistically significantly associated with PFS. The risk of death for patients from the high-PIV group (cut-off point: 548) was 3.4 times higher than for those with lower PIV values. The corresponding risk of progression for patients from the high-PIV group was 2.2 times higher. The G8 geriatric screening tool was not identified as a prognostic factor.

Conclusions: Lower PIV and obesity are associated with longer OS in geriatric mRCC patients treated with TKIs in the first line. These factors may be considered while making treatment decisions if further studies show the same results.

Primary pulmonary Hodgkin's lymphoma (PPHL) is a rare subtype of lymphoma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin- Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic workup involving a multidisciplinary team of clinicians, radiologists, and pathologists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists.

Melanomas are known for their diverse morphological features, presenting a diagnostic challenge for pathologists. Uncommon variations of melanoma can exhibit distinct cytological and histomorphological characteristics, including ganglioneuroblastic differentiation. However, this phenomenon is extremely rare, with only a few documented cases. Here, we present a unique case of an occult metastatic melanoma with ganglioneuroblastic differentiation developing in a 76-year-old male. The diagnosis was based on histopathology, immunophenotyping, and molecular testing, which revealed SOX10 positivity and an NRAS mutation. Notably, classic melanoma markers HMB45 and melan-A were negative, highlighting the importance of considering alternative markers. This case emphasizes the significance of immunohistochemistry and molecular investigation in diagnosing melanomas with unusual features and identifying appropriate candidates for immune checkpoint therapy. Additionally, the occurrence of ganglioneuroblastic differentiation further supports a shared histogenetic origin from the neural crest. Improved understanding of such rare variants contributes to accurate diagnosis and optimal management of melanoma patients.