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Histological transformation from non-small cell lung cancer to small cell lung cancer in patients with osimertinib treatment failure
No full textHistological transformation of NSCLC with EGFR mutations is a mechanism of an acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). The aim of the study is to analyze the clinical features of a patient diagnosed with advanced NSCLC, as well as the mechanism of histological transformation to small cell lung cancer (SCLC) after osimertinib treatment. In a 59-year-old non-smoking, female patient imaging tests showed the presence of a tumors in the left lung and a metastatic lesion in the right cerebellar hemisphere. The bronchofiberoscopy was performed and the histopathological result indicated adenocarcinoma. In this material, deletion in exon 19 of EGFR gene was detected. The treatment started with stereotactic radiotherapy of the central nervous system (CNS), and then the patient was qualified for treatment with osimertinib. During the therapy, adverse effects of osimertinib were observed in the form of hepatotoxicity and interstitial pneumonia. Initially, the disease remission and then stabilization were noted, but after 12 months the progression occurred. The material collected during the second bronchoscopy confirmed new recognition — neuroendocrine small cell lung cancer (SCLC) with endured presence of deletion in exon 19 of EGFR gene. The patient was qualified for second-line chemotherapy with cisplatin and etoposide. Early treatment tolerance was good and partial response was noted. It should be emphasized that the transformed tumor retained the original EGFR mutation, which confirms that the histological transformation was an evolution from the primary tumor. The re-biopsy should always be considered in NSCLC patients when EGFR-TKIs therapy is ineffective, in order to determine resistance mechanisms and to select the right therapeutic strategy
Association between gut microbiome components and immunotherapy efficacy in two small cell lung cancer cases with divergent outcomes
No full textIntroduction. Immunotherapy can be effective in some patients with small-cell lung cancer (SCLC) with good performance status. However, the factors contributing to sustained treatment responses remain unclear. The intestinal microbiome profile has emerged as a potential biomarker for the effectiveness of chemoimmunotherapy in SCLC. Evidence suggests that microbiome diversity, both in richness and abundance, may influence immunotherapy outcomes. The presence or absence of specific bacterial populations may also be linked to treatment success or failure. This pilot study compared the gut microbiome profile in two SCLC patients with partial responses to chemoimmunotherapy but had distinctly different outcomes.
Material and methods. Metagenomic analysis of the gut microbiome was performed using stool samples from two patients collected prior to treatment initiation. Gut microbiome composition was determined based on next-generation sequencing of the hypervariable regions of the 16S rRNA gene. Both patients received a treatment regimen consisting of atezolizumab, carboplatin and etoposide.
Results. The progression-free survival (PFS) and overall survival (OS) were 5.7 and 10.2 months for the first patient and 19.9 and 34.9 months for the second patient, respectively. The patient with early progression exhibited reduced species-level diversity compared to the long-term responder. Additionally, bacteria from the families Lachnospiraceae, Akkermansiaceae were found to be more prevalent in the patient with greater immunotherapy benefit. Conversely, the families Enterobacteriaceae, Succinivibrionaceae, Streptococcaceae, and Desulfovibrionaceae were more abundant in the patient with short survival than in patients with prolonged response.
Conclusions. Bacteria residing in the gut may affect the efficacy of chemoimmunotherapy in SCLC patients and represents a promising candidate for predictive biomarkers of treatment response and efficacy
Extraskeletal mesenchymal chondrosarcoma: oligometastatic disease and effect of multimodal treatment
No full textA 24-year-old female was diagnosed in 2018 with extraskeletal mesenchymal chondrosarcoma (MCS) of the left elbow (4 × 5 × 3 cm, antecubital fossa). TRU-CUT biopsy confirmed diagnosis neoadjuvant 3D conformal radiotherapy (RT) (25 Gy in 5 × 5 Gy fractions) was followed by R0 resection. Adjuvant chemotherapy (CHT) (VADRIAC: vincristine, actinomycin D, doxorubicin, ifosfamide, cyclophosphamide) was initiated. In Dec 2018, CT revealed pulmonary M1; thoracotomy achieved R0 resection of three nodules. CHT continued with EIAO (etoposide, ifosfamide, adriamycin, vincristine; total doxorubicin 1010 mg). FISH analysis excluded NR4A3 and DDIT3 rearrangements, confirming extraskeletal MCS (SOX9+, SOX10–). Platinumbased CHT (cisplatin–etoposide) was introduced. progressive disease (PD) in lungs by RECIST 1.1 (June 2019) led to first-line palliative CHT with gemcitabine (900 mg/m², D1 + 8) and docetaxel (75 mg/m², D8), achieving partial response (PR). In early 2020, liver M1 appeared (up to 24 × 19 mm). A second pulmonary metastasectomy was performed (December 2020). With further PD (mid-2021), VAI (vincristine, actinomycin D, ifosfamide) was administered for 7 cycles, achieving PR. Due to isolated mediastinal progression, RT (45 Gy in 15 × 3 Gy fractions) was delivered (October 2021) resulting in PD. Temozolomide-irinotecan failed (PD), as did rechallenge with gemcitabine-docetaxel (PD, January 2022). In Mar 2022, the patient developed symptomatic CNS metastases (largest 23 × 22 mm, frontoparietal region). Palliative care was initiated, and she died at home shortly after. The patient underwent eight systemic regimens over four years with initial PRs but eventual PD and CNS involvement
Polekowa niedokrwistość immunohemolityczna — wpływ wybranych leków na badania immunohematologiczne
No full textDrug-induced immune hemolytic anemia is a rare condition. It is difficult to distinguish from hemolytic anemias of other etiologies, which delays diagnosis and treatment. In cases of a positive direct antiglobulin test and negative elution results, the influence of a drug should be considered. A thorough clinical history is crucial to exclude other causes of anemia. This paper discusses the mechanism, diagnostic tests, and treatment of drug-induced hemolytic anemia. Examples of drugs most commonly reported as causes of anemia are also presented.Niedokrwistość immunohemolityczna zależna od leku jest rzadką chorobą. Jest trudna do odróżnienia od niedokrwistości hemolitycznych o innej etiologii, co opóźnia diagnostykę i leczenie. W przypadku dodatniego bezpośredniego testu antyglobulinowego i ujemnych wyników elucji należy rozważyć wpływ leku. Dokładny wywiad kliniczny jest decydujący w celu wykluczenia innych przyczyn niedokrwistości. W niniejszej pracy omówiono mechanizm, badania oraz leczenie polekowej niedokrwistości hemolitycznej. Przedstawiono również przykłady leków najczęściej opisywanych jako przyczyny niedokrwistości
Asciminib — skuteczna opcja terapeutyczna u pacjenta z przewlekłą białaczką szpikową i nadciśnieniem płucnym
No full textWprowadzenie: Leczenie przewlekłej białaczki szpikowej (CML) opiera się na terapii celowanej inhibitorami kinaz tyrozynowych (TKIs). Stosowanie poszczególnych TKIs jest wysoce skuteczne i umożliwia osiągnięcie głębokiej odpowiedzi molekularnej. Ze względu na przewlekły charakter terapii pacjenci z CML są jednak narażeni na wystąpienie toksycznych powikłań, które mogą istotnie obniżać jakość życia. Jednym z takich powikłań jest nadciśnienie płucne, obserwowane przede wszystkim podczas terapii dazatynibem.
Nowym inhibitorem kinazy tyrozynowej bcr-abl1 jest asciminib, działający w odmienny sposób od dotychczas stosowanych TKIs. Charakteryzuje się on korzystnym profilem bezpieczeństwa i obecnie znajduje zastosowanie u chorych na CML po nieskuteczności lub nietolerancji co najmniej dwóch TKIs.
Opis przypadku: Opis przypadku dotyczy młodego pacjenta z CML, u którego w trakcie leczenia dazatynibem rozwinęło się nadciśnienie płucne. Zmiana terapii na asciminib doprowadziła do uzyskania odpowiedzi hematologiczno-molekularnej oraz ustąpienia toksyczności kardiologicznej
Neoadjuvant immunotherapy in non-small cell lung cancer — a comprehensive literature review
No full textNeoadjuvant immunotherapy has emerged as a transformative approach in the treatment of resectable non-small cell lung cancer (NSCLC), offering significant improvements in pathological response rates and event-free survival compared to traditional chemotherapy. This comprehensive review synthesizes findings from major phase II and III clinical trials, including CheckMate 816, KEYNOTE-671, AEGEAN, NADIM II, and SAKK 16/14, as well as meta-analyses evaluating various immunotherapy regimens. The evidence demonstrates that neoadjuvant immunotherapy, particularly in combination with chemotherapy, enhances major pathological response (MPR) and pathological complete response (pCR), leading to improved long-term outcomes. Subgroup analyses have identified specific patient populations, such as those with high PD-L1 expression, who derive the most benefit, while challenges remain in predicting response among patients with EGFR mutations or never-smokers. Safety analyses confirm the manageable toxicity profile of immunotherapy, though immune-related adverse events occur more frequently than with chemotherapy alone. Despite its promise, several challenges persist, including optimizing treatment duration, standardizing response assessments, and identifying robust predictive biomarkers. Circulating tumor DNA (ctDNA) has shown potential as a biomarker for treatment response, yet further validation is required. Future research should focus on refining patient selection criteria, improving combination strategies, and evaluating long-term survival outcomes through extended follow-up studies. In conclusion, neoadjuvant immunotherapy represents a paradigm shift in the management of resectable NSCLC, offering new hope for improved survival. Continued investigation and refinement of therapeutic strategies will be essential to maximizing its clinical impact
The use of stereotactic radiotherapy in the treatment of lung malignancies — a scoping review
No full textIntroduction. Lung cancer remains as main cause of cancer-related mortality, despite new advances, with many patients remaining inoperable. Novel methods of radiotherapy, including stereotactic body radiotherapy (SBRT), can provide survival benefits in lung cancer, mainly in inoperable patients. However, its use in many forms of lung cancer is still heavily debated. To this end, the present scoping review was undertaken to assess the clinical outcomes of stereotactic radiotherapy in patients with lung cancer.
Material and methods. Major electronic databases were searched using keywords and Boolean operators for relevant records. Records were filtered according to the PRISM-ScR guidelines and eligible records were selected. Data regarding clinical outcomes, including the survival rate and toxicities, were extracted from each included study.
Results. The literature search retrieved a total of 16,006 records, out of which 15 were included in the synthesis of the review. Stereotactic body radiotherapy showed favorable results in patients with non-small lung cancer as well as patients with bronchial carcinoid tumors and other subtypes of lung cancer, with few significant toxicities reported.
Conclusions. Stereotactic body radiotherapy can be further implemented for clinical use in patients with different subtypes of lung cancer. Nevertheless, further research is required to establish standardized dosing protocols, improve toxicity reporting, and explore SBRT’s role in more complicated and rare cases
Hemochromatosis — an insidious genetic disease
No full textHemochromatosis is a genetic disorder inherited in an autosomal recessive pattern. The mostfrequent forms of hereditary hemochromatosis include hemochromatosis with a mutation inboth alleles of the HFE gene — homozygotes with the C282Y mutation and C282Y/H63D heterozygotes.The mutation results in iron overload due to a deficiency of the protein — hepcidin.The symptoms of the disease manifest quite late, i.e., in the 40s or 50s. Hemochromatosis is a multifactorialand multi-organ disease, affecting the liver, heart, pancreas and joints, among others.The key to the diagnosis of hereditary hemochromatosis is a serum ferritin level > 1000 ng/ml,TSAT > 45% and genetic test result confirming a mutation in the HFE gene. The most commonmethod of treatment is phlebotomy, or so-called blood-letting. With early diagnosis andtreatment, serious complications can be prevented and, consequently, with appropriate treatment,the life expectancy of people with hereditary hemochromatosis does not differ from thatof the general population