Abstracts for the National Congress of Oncology

CT-guided bone biopsy – the only diagnostic solution in small tumors

 

Răzvan Adam, Alnuaimi Osama

“Elias” University Emergency Hospital, Bucharest; Memorial Hospital Băneasa, Romania

 

Bone tumor biopsies, performed percutaneously, needle-harvested, computed tomography (CT) guided, are a safe and accurate method for obtaining a diagnosis of primary or secondary bone lesions. This method has a low complication rate, a low morbidity and a low cost compared to incisional biopsy. Although classical, incisional biopsy is still considered the standard, in the case of small tumors or in those difficult to approach by the open method, CT-guided needle biopsy is the only diagnostic option. In a period of 19 months, between January 2022 and August 2023, we performed 16 CT-guided needle bone biopsies at the Monza Oncology Hospital (Memorial), one of which was PET-CT guided and two were followed by radiofrequency ablation. All interventions had positive diagnostic results, identifying the tumor type and having an accuracy rate (histological diagnosis consistent with final diagnosis) of 89%. In conclusion, CT-guided bone biopsy is an accurate and efficient method, being the only diagnostic solution for small tumors, the limitation of the method being represented by the surgical technique and the personal experience.

Keywords: small bone tumors, biopsy, computed to­mo­graphy

 

Axitinib and sorafenib treatment inhibits high-grade glioma cell growth in vitro

 

Ştefan-Alexandru Artene^1,2, Alexandru Opriţa^1,4, Mihaela-Amelia Dobrescu³, Elena-Victoria Manea¹, Ştefana-Oana Popescu¹,
Elena-Luiza Artene⁴, Andreea-Silvia Pîrvu¹, Iuliana-Mihaela Buzatu⁵, Daniela-Elise Tache¹, Anica Dricu¹

1. Department of Biochemistry, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

2. Laboratory of Radiology and Medical Imaging, County Emergency Clinical Hospital Craiova, Romania

3. Department of Medical Genetics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

4. Medical Oncology Clinic, County Emergency Clinical Hospital Craiova, Romania

5. Department of Pharmacological Technology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania

 

The formation, proliferation and evolution of glioblastoma (GBM) are significantly influenced by pathologic angiogenesis. This is supported by several growth factor receptors, such as the vascular endothelial growth factor receptor (VEGFR). In this experiment, we examined how the Food and Drug Administration (FDA) approved VEGFR blockers sorafenib and axitinib affect the viability of GBM cells in vitro. Cells have been cultivated in 96-well culture plates for the experiments, afterwards sorafenib and axitinib were administered at doses ranging from 0.3 μM to 80 μM. MTT assay was used to assess the impact of VEGFR inhibition on high-grade glioma (HGG) cell lines. To observe the morphological changes in cell shape, we used a 10x magnification microscopy. Our results showed that both axitinib and sorafenib hindered GB1B culture proliferation in a dose-dependent and time-dependent manner, in comparison to control cohorts that had not received any treatment. The IC50 value for axitinib was 3.5839 μM after three days of drug administration and 2.2133 μM after seven days of drug administration, while for sorafenib, it was 3.5152 μM after three days of drug administration and 1.6846 μM after seven days of drug administration. After the treatment with axitinib or sorafenib, very few cells became rounded and detached from the support, others remained adherent to the culture substrate, but acquired a larger, flatter shape. Our results suggest that VEGFR may serve as an important target in the treatment of GBM. A better understanding of the mechanisms of resistance to VEGF/VEGFR inhibitors and the identification of effective treatments after progression are now critically needed for patients with GBM.

Keywords: axitinib, sorafenib, high-grade glioma, in vitro

 

Current standard of care and recent progress in recurrent/metastatic endometrial cancer

 

Maria-Alexandra Barbu

Eight Department of Radiology, Oncology and Hematology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest; MedEuropa Center of Oncology and Radiation Therapy, Bucharest, Romania

 

Endometrial cancer is the sixth most common female tumor, with both incidence and mortality increasing worldwide. Although the localized disease is curable by surgery, with a five-year overall survival rate of 96%, in advanced stages the five-year survival rate drops to less than 20%. Platinum-based chemotherapy represented the standard of care in first-line chemotherapy, but 50% of patients progressed within one year. Today, because of the newest classification of four molecular subgroups of endometrial cancer, we can identify patients who can benefit from immunotherapy or targeted therapy, and we can offer those women a longer overall survival rate, with a better quality of life. The recent advances in immunotherapy opened other options for women with the MSI subset of tumors and, given the wealth of targets in endometrial cancer, the challenge will be to choose the proper treatment and sequencing to obtain the best outcome in the first or second line of therapy for our patients. Since endometrial cancer is the only gynecologic cancer with an increasing incidence and death rate, it is crucial to identify effective treatments and to find therapeutic combinations that can improve the medication performance while reducing drugs toxicities.

Keywords: endometrial cancer, targeted therapy, immunotherapy

 

Emerging roles of mRNA/miRNA/lncRNA networks in non-small cell lung cancer

 

Cecilia Bica, Cornelia Braicu, Lajos Ráduly, Cristina-Alexandra Ciocan, Ioana-Berindan Neagoe

Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

 

Introduction. Lung cancer represents the second most diagnosed cancer worldwide and is the leading cause of cancer death. Considering the involvement of noncoding RNAs in various cancer-related processes, the idea of an interaction between these molecules arose. This study focused on identifying a lncRNA-miRNA-mRNA network with connection to biological processes altered in lung cancer. Using this approach, we aimed to identify potential targetable molecules to improve lung cancer patients’ response to therapy and, thus, their survival rate. Materials and method. In silico analysis for identification of differentially expressed miRNAs, lncRNAs and mRNAs and subsequent survival analysis of LUAD and LUSC TCGA datasets were performed. The interconnection among these transcripts was emphasized. Correlation analysis of mRNA/miRNA/lncRNA pairs in lung cancer was performed. Validation of mRNA/miRNA/lncRNA expression using two independent cohorts of LUAD and LUSC patients in a qRT-PCR experiment was performed. Results. We identified top dysregulated mRNA/miRNA/lncRNA transcripts in LUAD and LUSC TCGA datasets. Survival analysis on TCGA datasets based on the expression of the selected dysregulated transcripts allowed the identification of potential mRNA/miRNA/lncRNA pairs with prognostic biomarker potential. The expression pattern of the mRNA/miRNA/lncRNA in the TCGA datasets was confirmed in qRT-PCR experiments performed on LUAD and LUSC patient cohort. Conclusions. RNA networks in cancer have clinical value in various aspects of patient care, including diagnosis, prognosis, treatment stratification and monitoring. The study revealed differences in terms of molecular imbalance in the two subtypes of NSCLC.

Keywords: mRNA/miRNA/lncRNA, prognostic biomarkers, non-small cell lung cancer

 

Applications of functional genomics to assess the impact of environmental toxic agents on human health

 

Cornelia Braicu¹, Oana Zănoagă¹, Cristina Ciocan¹, Lorena-Lavinia Pruteanu^1,2, Raduly Lajos¹, Ioana Berindan-Neagoe¹

1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. Department of Chemistry and Biology, North University Center at Baia Mare, Technical University of Cluj-Napoca, Romania

 

Functional genomics approaches are widely used to assess the toxicity of environmental toxic agents. It can be used to identify changes in transcriptomic profile associated with exposure to these environmental agents, helping to understand the mechanisms of toxicity and to predict potential health risks. The evaluation of biological response has applications in toxicology, biomarker discovery, epidemiology, drug development and environmental monitoring. Using functional genomics approaches contributes to a better understanding of the complex interactions between the environment and human health. We present some showcase transcriptomic data (microarray gene and miRNA expression), revealing specific responses associated with exposure to arsenic, cadmium and lead on normal and tumoral cell lines. These responses can serve as biomarkers of exposure, making them valuable tools for identifying environmental issues. We were able to identify the molecular pathways activated in response to these contaminants by short- or long-term exposure experiments, contributing to our understanding of the complex interactions between the environment and the human health. This underscores the significance of these state-of-the-art approaches in enhancing our understanding of the complex relationship between the exposure to toxic environmental agents and the human health.

Keywords: functional genomics approaches, toxic environmental agents, potential health risks

 

The role of multi-miRNAs panels in identifying common features in lung adenocarcinoma and lung squamous cell carcinoma patients

 

Liviuţa Budisan¹, Ioana Iurca^1,2, Ecaterina Isăcescu¹, Cecilia Bica¹, Antonia Haranguş³, Cornelia Braicu¹, Ioana Berindan-Neagoe¹

1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. Oncology Department, “Dr. Constantin Opriş” County Emergency Clinical Hospital, Baia Mare, Romania.

3. Bronchology Department, “Leon Daniello” Clinical Hospital of Pneumophthisiology, Cluj-Napoca, Romania

 

While cancer continues to put pressure on the global health system due to its increase in incidence and mortality, lung cancer contributes to this threat with the highest number of new patients diagnosed each year, especially in late stages, causing a high rate of patients dying from this disease, still with limited therapeutic options, despite some progress made for targeted therapies and actionable genes. The high toxicity capacity of systemic drugs remains dramatic for the patient’s quality of life. Considering this context, our growing interest in the last decade is focused on investigating noncoding RNAs and their target/targeted genes in many cancers and cancer subtypes. We investigated a cohort of lung cancer patients suffering from NSCLC, using tumor tissue and adjacent nontumoral tissue for the expression level of three miRNAs. These short sequences 19-24 are conserved during tissue evolution and can be used as good-quality specimens for showing the relation with their target genes. We evaluated the expression level of miR-96-5p, miR-144-3p and miR-210-5p for lung adenocarcinoma and squamous cell carcinoma patients. Two miRNAs showed statistical significance in both histological subtypes, making them optimal candidates to accompany the pathological diagnosis, improving the active pathways involved in tumor evolution. Our data have shown a p-value of 0.0001 for miR-96-5p and 0.0007 for miR-210-5p in LUSC. In LUAD, values were 0.0018 for miR-96-5p, and 0.0007 for miR-210-5p. MiR-144-3p was not statistically significant, potentially due to the number of patients investigated. We propose these miRs for molecular support in NSCLC diagnosis, opening the way for targeted and targeting genes for these miRs.

Keywords: multi-miRNAs panels, lung adenocarcinoma, lung squamous cell carcinoma

 

TIL immunotherapy – progress or necessity of science?

 

Alexandra Căţoiu, Maria-Cristina Orlov-Slavu

“Elias” University Emergency Hospital, Bucharest, Romania

 

In 2022, more than 100,000 cases of melanoma were reported, leading to more than 15,000 deaths, mostly in adult men. Immunotherapy has increased the survival rate of patients with metastatic disease but, despite these advances, many patients will relapse. Thus, the development of additional therapeutic options was imperative. This is how TIL immunotherapy was developed, consisting of lymphocytes with the ability to infiltrate the tumor. These lymphocytes are extracted from the patients’ body, grown to very large numbers in a laboratory with interleukin-2 and infused back into the body where they actively attack cancer cells. Next, we will present the case of a 62-year-old male treated with adjuvant PD-1 inhibitor, who subsequently progressed with bone metastases. The BRAF V600E mutation was identified and BRAF/MEK inhibitor was chosen, but new oncological lesions appeared shortly after, located subcutaneous and in the testicles. We switched to anti-PD-1 combined with CTLA4 for four cycles, remaining in maintenance with anti-PD-1. Although the clinical benefit existed, new lesions appeared in the adrenal glands and peritoneum. The patient was referred to TIL therapy which he underwent in August 2023. He presented 10 days after the completion of TIL with complete clinical regression of two 2/3 cm subcutaneous masses. The patient will continue maintenance therapy with anti-PD-1 and he will be followed-up closely both clinically and by imaging.

Keywords: immunotherapy, survival, case pre­sen­tation

 

Triple-negative breast cancer with brain metastases and recurrent pulmonary invasive aspergillosis – a therapeutic challenge

 

Ioana-Roxana Cârlan, Eva-Maria Cojocaru

Regional Institute of Oncology, Iaşi, Romania

 

Introduction. Invasive pulmonary aspergillosis (IPA) is a serious fungal infection, a major cause of mortality in immunocompromised patients, especially in those with underlying pulmonary disease. The most afflicted categories are: patients with AIDS, hematologic malignancies, transplant recipients, those with a history of chest radiotherapy, prolonged neutropenia or with a history of corticosteroids use. Case presentation. A 44-year-old premenopausal woman, with no significant hereditary or personal pathological history, was diagnosed with stage IIIA left breast cancer. She had received a neoadjuvant dose-dense epirubicin-cyclophosphamide (EC) regimen, with growth factor support, followed by weekly paclitaxel, with corticosteroids support as premedication for the prophylaxis of taxane hypersensitivity reactions, for 11 weeks. In her last chemotherapy cycle, she presented fever, dyspnea, loss of appetite with weight loss, her vital signs being as follows: temperature 39°C, blood pressure 139/77 mmHg, pulse 107 beats/min, and O₂ saturation of 97% on room air. On auscultation, we noticed diminished vesicular murmur bilaterally. The laboratory results revealed grade 3 lymphopenia and an elevated CRP level (120 mg/l), with negative urine cultures and negative tests for respiratory syncytial virus, influenza A/B and SARS-CoV-2. The cardiological evaluation ruled out a cardiac cause of dyspnea. Chest CT revealed nonspecific interstitial pneumonia (NSIP) with subpleural fibrosis, and broad-spectrum antibiotic therapy was initiated, but with the persistence of the febrile syndrome. The patient underwent bronchoscopy and bronchoalveolar lavage, positive for Pneumocystis jiroveci and Aspergillus. Based on these results, we decided on antibiotic treatment with Tienam®, linezolid and TMP/SMX and antifungal therapy with voriconazole, with improved clinical and biological status. After two months, the patient underwent radical mastectomy, with nonpathological complete response. Next, she received adjuvant chemotherapy with capecitabine and external adjuvant radiotherapy. After another three months, the patient was diagnosed with brain metastases and she underwent external palliative radiotherapy. During her hospitalization in the radiotherapy department, she developed respiratory symptoms, being again diagnosed with invasive pulmonary aspergillosis, with a more severe evolution than in the first episode. In the context of this pulmonary complication, both the curative treatment and the treatment for the metastatic disease were delayed. We mention that the patient had PD-L1 and BRCA negative status. In both scenarios, the therapy would have been a real challenge. If the patient had a BRCA mutation, the use of olaparib would have required caution regarding the concomitant administration of strong in­hi­bitors of CYP3A enzyme, such as voriconzole. Also, the immunotherapy use would have been difficult to manage, with this atypical respiratory infection with reactivations, but we cannot talk about therapeutic safety neither using again the chemotherapy regimens. Discussions. The prognosis of invasive pulmonary aspergillosis is poor, despite antifungal therapy options. In patients with solid tumors, there is still a lack of data, with nonspecific symptoms and imaging, but usually the dose-dense regimens, especially with corticotherapy use, have a major risk. In some cases, corticotherapy can mask the symptoms, which delays the diagnosis of aspergillosis.

Keywords: triple-negative breast cancer, brain meta­stasis, case presentation, pulmonary aspergillosis

 

Exploring therapeutic pathways for recurrent testicular seminoma in young patients: a case report on salvage treatments

 

Irina-Alexandra Chirea¹, Adelina-Silvana Gheorghe^1,2, Elena-Adriana Dumitrescu^1,2, Crina-Maria Siminiceanu¹, Mihai Bălaşa¹,
Lidia-Anca Kajanto¹, Raluca-Ioana Mihăilă^1,2, Daniela Zob¹, Dana-Lucia Stănculeanu^1,2

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

Introduction. Testicular cancer is a relatively rare but highly curable malignancy, with seminoma being one of its most common histological subtypes. This complex case presentation highlights the evolution of a 34-year-old patient who was diagnosed with testicular seminoma. Case presentation. The patient underwent a radical inguinal orchiectomy in August 2021, the standard surgical approach for testicular cancer. Following surgery, the computed tomography (CT) scan revealed the existence of lymph node metastasis – stage IIC, pT3cN3M0 S1, and he began the treatment with first-line chemotherapy (four cycles of EP). Post-chemotherapy, PET-CT confirmed the residual disease, and retroperitoneal lymph node dissection was performed. Afterwards, the CT scan showed the rapid progression of the disease (lymphatic metastasis), with the increase of lactate dehydrogenase. Thereby, the second line of chemotherapy was started (four cycles of TIP). After six months, lymphatic, pleural, pulmonary, hepatic, peritoneal and bone metastasis were noted, and he was proposed for another platinum-based therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). The salvage chemotherapy was initiated with CBOP/BEP protocol, with weekly administration, and a partial initial response was noted. Bone marrow biopsy was performed but, unfortunately, the histopathological exam proved the extension of the disease to the bone marrow, therefore the ASCT was no longer feasible. The patient experienced a rapid progression in the following months, complex palliative care for pain control, and he eventually died. Conclusions. While salvage therapies remain an essential component in the treatment arsenal for testicular seminoma, their limitations point to a pressing need for innovation and individualized treatment strategies to improve the prognosis for this challenging patient population. Unfortunately, in patients with relapse after salvage chemotherapy or with cisplatin-refractory disease, the cure is infrequently achieved.

Keywords: recurrent testicular seminoma, young patient, salvage treatment

 

Alteration of the miR-21, miR-155 and miR-181a expression level in breast cancer: implications in the immune response and possible prognostic value

 

Paul Chiroi¹, Ecaterina Isăcescu¹, Monica Groza², Cristina Ciocan¹, Cecilia Bica¹, Ovidiu-Laurean Pop³, Cornelia Braicu¹,
Ioana Berindan-Neagoe¹

1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. Department of Medical Oncology, “Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, Romania

3. Department of Morphological Sciences, Faculty of Medicine and Pharmacy, University of Oradea, Romania

 

Breast cancer is the most common neoplasm worldwide, with more than 2.2 million cases and 680,000 deaths each year. Despite all clinical advances, the prognosis of patients with metastatic disease remains poor, with a five-year survival rate of 25%. Breast tumors profiling has led to the association of microRNAs with various biological processes such as the immune response, a reaction specific to early stages, highlighting their potential as prognostic biomarkers. In this regard, based on a molecular interaction network and on an in silico expression analysis, our study evaluated the abundance level of miR-21-5p, miR-155-5p and miR-181a-5p, looking for its correlation with the immune profile rendered by CCL20, EGR1, TGF-b and TNF-a genes in 30 cases of stage T1/2 breast cancer. According to our results, both the panel of microRNAs and genes associated with proinflammatory reactions were found to be overexpressed in tumor tissues compared to non-tumoral ones. Moreover, according to literature, CCL20, EGR1, TGF-b and TNF-a genes are involved in the pathogenesis and progression of breast cancer. Therefore, the overexpression of miR-21-5p, miR-155-5p and miR-181a-5p could have a negative prognostic value in early stages and could help stratify patients. However, our observations require further validations.

Keywords: miR-21, miR-155, miR-181, breast cancer, immune response

 

Successive pulmonary metastasectomies and an unusual adverse reaction in a patient with renal neoplasm: a case study

 

Enache Cioc¹, Iolanda Goga¹, Mihaela Moraru¹, Monica-Adriana Nichita¹, Daniela-Luminiţa Zob¹, Ionuţ Chira², Mihnea-George Orghidan³

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Prof. Dr. Theodor Burghele” Clinical Hospital, Bucharest, Romania

3. “Marius Nasta” Institute of Pneumophthisiology, Bucharest, Romania

 

Clear cell renal cell carcinoma is described in the medical literature as a pathology with a high rate of distant metastases, even in patients initially presenting with localized disease at the time of diagnosis. We present the case of a 75-year-old woman who presented in June 2016 to the oncology department with a diagnosis of chromophobe cell renal cell carcinoma, previously treated with radical nephrectomy in 2006, and a pulmonary metastasis that was surgically removed in May 2016, with histopathological and immunohistochemical aspect of clear cell renal cell carcinoma. As the resection margins of the metastasectomy were negative, a decision was initially made to perform periodic imaging follow-up. In June 2017, a new pulmonary nodule was identified on a CT scan, leading to a second surgical intervention with complete excision, histopathologically confirmed as a new metastatic lesion. We maintained the same therapeutical approach until November 2021 when a new pulmonary nodule was detected on a CT scan. Resection followed by histopathological examination established the same diagnosis, but this time with positive macroscopic and microscopic resection margins. The patient met the criteria for the intermediate-risk group and began the treatment with axitinib and avelumab in July 2022. The treatment was poorly tolerated, with the patient experiencing severe bilateral visual impairment, with ophthalmologic examination establishing the diagnosis of keratoconjunctivitis sicca. The treatment was temporarily discontinued, with partial improvement of the symptoms, but which worsened upon treatment resumption. Subsequent imaging evaluations revealed disease progression involving the pancreas, bones and liver. The patient refused a new biopsy of the lesions and, therefore, a decision was made to initiate the second-line therapy with cabozantinib in May 2023, which has been continued to the present day, with good clinical tolerance and with improvement in visual disturbances. This case highlights the success of metastasectomies in providing a six-year interval between the appearance of the first metastatic lesions and the initiation of systemic therapy. It also underscores the development of a rare but debilitating adverse reaction.

Keywords: clear cell renal cell carcinoma, metastasectomy, keratoconjunctivis sicca

 

Fluoropyrimidine-induced cardiac toxicity: challenges and treatment opportunities. Case report

 

Maria-Loredana Ciontea¹, Elena-Adriana Dumitrescu^1,2, Crina-Maria Simiceanu¹, Anca-Alexandra Stolojanu¹, Radu Matei¹,
Adelina-Silvana Gheorghe^1,2, Irina-Alexandra Chirea¹, Sânziana Prundianu¹, Dana-Lucia Stănculeanu^1,2

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

This case report aims to present the importance of car­diac evaluation in patients with advanced colorectal can­cer and how to adjust the treatment according to cardiac patho­logy. A 60-year-old female patient, with a perso­nal history of breast cancer, presented in our clinic in August 2020 with resected rectal adenocarcinoma, with poorly differentiate histology obtained from the surgical specimen (June 2020). She received adjuvant therapy with capecitabin (six cycles) and radiotherapy. In July 2022, the PET scan revealed enlarged retroperitoneal lymph nodes with high metabolic activity. In October 2022, the patient received radiotherapy at the level of adenopathies in the renal hilum adenopathies with a total dose of 30 Gy, with good tolerance. In November 2022, she started chemotherapy with FOLFOX and bevacizumab. Suddenly after that, she was diagnosed with inferior myocardial infarction. Given the cardiac pathology and the oncological treatment, the patient was considered to be at a very high risk for cardiac toxicity. The cardiologist recommended close surveillance of the cardiac function, stopping the therapy with known cardiac toxicity (coronary vasospasm) such as fluoropyrimidines and continuing bevacizumab with caution. Every three months, she had a cardiac evaluation and the patient was stationary, without severe cardiac dysfunction. The oncological treatment continued since February 2023, but it was adjusted (only oxaliplatin 85 mg/m² and bevacizumab, initially 5 mg/kg b.w., and then an increased dose at 7.5 mg/kg b.w.). The evolution was favorable, the imagistic evaluation from May 2023 showing the regression of the retroperitoneal adenopathies. Currently, she is at the 11^th series with oxaliplatin in monotherapy, with good tolerance. Fluoropyrimidines, such as fluorouracil, are associated with vasospasm and can produce myocardial infarction, especially in patients with poor adherence to cardiological treatment. There is a high recommendation for cardiac function monitoring in patients receiving oncological treatment.

Keywords: advanced colorectal cancer, poorly differen­tiated histology, inferior myocardial infarction, cardiac toxicity, fluoropyrimidines, cardiac evaluation

 

How calm should I keep? Café-au-lait macules as potential manifestations of cancer susceptibility syndromes

 

Andrei Cismaru, Ioana Berindan-Neagoe

Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

 

Objectives. Café-au-lait macules (CALMs) are common findings in 10-36% of healthy individuals. However, CALMs may represent a skin manifestation in more than 60 genetic syndromes, some of which may associate a predisposition to the development of cancer. The aim of the present study was to identify syndromes with a genetic predisposition to cancer, which are associated with CALMs. Materials and method. We interrogated the OMIM (Online Mendelian Inheritance in Man) database to identify cancer susceptibility syndromes that associate CALMs within their phenotype. The terms “café-au-lait” and “malignant” were used, and for each recognized syndrome we identified the gene involved, the chromosomal locus, the type of transmission, the associated skin manifestations and the main malignant tumors associated with the syndrome. Results. Fifteen genetic cancer susceptibility syndromes have been identified that associate CALMs as skin manifestations. These are neurofibromatosis type 1 and 2, Nijmegen syndrome, mismatch repair cancer syndrome 1, 3 and 4, Bloom syndrome, Rubinstein-Taybi syndrome type 1, ataxia-telangiectasia, multiple endocrine neoplasia type 1 (MEN-1), McCune-Albright syndrome, Fanconi anemia complementation group A, Noonan syndrome type 1, Van Asperen syndrome, and pheochromocytoma. Conclusions. By developing a custom panel of next-generation sequencing for the genes involved in the pathogenesis of cancer predisposition syndromes, genetic testing in children presenting with CALMs could represent a valuable tool for pediatric oncohematologists and will help avoid life-threatening complications.

Keywords: café-au-lait macules, cancer susceptibility syndromes, genes in pathogenesis

 

Good clinical response to treatment with cemiplimab in the case of a patient with cutaneous squamous cell cancer with recessive dystrophic epidermolysis bullosa

 

Simina Condruz

MedLife Hospital, Braşov, Romania

 

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by the defect or absence of type VII collagen. This leads to skin fragility patients presenting lesions at minor injuries with difficult healing. Cutaneous squamous cell carcinoma (SCC) is more frequent in patients with this genetic disease than in the general population because of the chronic wound formation, being an important cause of death for these patients. We present the case of a 19-year-old patient with RDBE and inoperable locally advance squamous cell carcinoma of the left upper limb. The treatment started was cemiplimab 350 mg i.v. every three weeks. An objective clinical response was observed after the second cycle of treatment, with no toxicity. During the follow-up, the patient had a notable clinical response, with no adverse reactions. This case shows that cemiplimab is an important therapy option for patients with cutaneous squamous cell carcinoma, with a good safety profile.

Keywords: cemiplimab, cutaneous squamous cell cancer, dystrophic epidermolysis bullosa

 

Brain tumors targeted therapy in the era of personalized oncology

 

Anica Dricu¹, Alexandra Costachi¹, Adeline Staicu¹, Amelia Dracea², Suzana Dănoiu³, Veronica Sfredel⁴, Ligia-Gabriela Tătăranu⁵

1. Department of Biochemistry, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

2. Department of Biophysics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

3. Department of Pathophysiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

4. Department of Physiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

5. Department of Neurosurgery, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

High-grade gliomas (HGGs) are the most aggressive and lethal brain tumors in adults. Although they are a group of malignancies that have many common alterations, due to the known heterogeneity of these tumors, particularities of each individual patient have also been observed, encouraging the personalized therapy. The goal of personalized medicine is to provide patients with the best care possible, based on their unique medical histories, physiological conditions and the molecular characteristics of their tumors. PDGFR changes were discovered in over 40% of HGGs. In adult high-grade gliomas, EGFR is overexpressed and amplified, and the response to targeted inhibition depends on the biology of the tumor. In addition, the EGFR mutation is linked to gliomagenesis, invasion and, ultimately, resistance to treatment modalities like chemotherapy and radiotherapy. Thus, growth tumor modeling and suppression, via targeted RTKs, represent an area of great interest. RTKs manipulation is also required because overexpession or constitutive activation of VEGFR, FGFR, PDGFR and IGFR, as well as other growth factor receptors are frequently observed in HGGs. As the overactivation of RTKs occurs, many downstream signaling pathways are activated, the major transduction pathways being represented by RAS/MAPK and PI-3 K/AKT. Small-molecule RTK inhibitors have been intensively researched as potential inhibitors for targeted therapies. Here, we discuss the progress in the field of small molecule RTK inhibitors used for the treatment of high-grade gliomas, in the era of personalized oncology.

Keywords: targeted therapy, personalized medicine, high-grade gliomas

 

Finding the optimal treatment sequence in metastatic castration-resistant prostate cancer – case report

 

Miruna Ghigeanu

Colţea Clinical Hospital, Bucharest, Romania

 

Introduction. The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has dramatically improved over the last decade; however, finding the optimal treatment sequence for these patients is still being investigated. Case report. We present the case of a 72-year-old patient who had an initial PSA level of 786 ng/mL and an Eastern Cooperative Oncology Group (ECOG) score of 0. The imaging studies indicated extraprostatic extension and seminal vesicles invasion. Multiple regional and distant lymph node metastases were also detected. Subsequently, prostatic biopsy revealed a poorly differentiated adenocarcinoma with a Gleason score of 8 (4+4). The patient was diagnosed with stage IVB adenocarcinoma of the prostate (cT3b cN1 M1a). After discussing the case in a multidisciplinary tumor board, the patient underwent external beam radiotherapy (EBRT) together with ADT: bicalutamide combined with goserelin treatment (the patient refused chemotherapy with docetaxel). After nine months of ADT treatment, the disease progression occurred: the PSA level increased to 250 ng/mL (after regression to 40 ng/mL during the treatment) and the patient developed multiple lymph node and bone metastases. The testosterone levels suggested mCRPC. The patient declined docetaxel administration and opted for abiraterone plus prednisone treatment, in addition to goserelin. Zoledronic acid was also administered. The treatment was well tolerated for a period of ten months, with subsequent PSMA-PET imaging revealing complete metabolic response. Unfortunately, disease progression reoccurred: the PSA level increased to 300 ng/ml and both lymph node and bone metastases progressed on imaging scans. Following the MDT recommendations, the patient underwent NGS testing, with results negative for mutations, including BRCA panel. The treatment was then switched to docetaxel and prednisone for six cycles, in addition to goserelin. Zoledronic acid was not administered due to patient’s ongoing dental procedures. The cycles were very well tolerated, with an ECOG score of 1 and a PSA response level of 113 ng/mL. Post-treatment reevaluation revealed rapid progression of the known metastases. The patient was then switched to enzalutamide after refusing chemotherapy with cabazitaxel. After three months of treatment with enzalutamide, progression occurred with newly diagnosed lung metastases, together with a rapid increase in the PSA level to 720 ng/ml. The patient was initiated on cabazitaxel treatment and he underwent three cycles with very low tolerance due to hematological toxicity, which resulted in treatment discontinuation. The patient was referred to a dedicated prostate cancer treatment facility, which recommended lutetium therapy. After undergoing three cycles of lutetium, a partial response to treatment was observed: the PSA level decreased to 250 ng/ml, the imaging showed partial remission, and the quality of life (QoL) did not decrease significantly. Conclusions. Given the growing incidence of mCRPC cases, a comprehensive care plan establishing the most successful treatment sequence is necessary, in order to achieve prolonged survivorship.

Keywords: mCRPC, treatment sequence, survivorship

 

From factor V Leiden mutation to vascular leiomyosarcoma – a medical challenge

 

Iolanda Goga¹, Mihaela Moraru¹, Enache Cioc¹, Adriana-Monica Nichita¹, Elena-Adriana Dumitrescu¹, Adelina-Silvana Gheorghe^1,2, Dana-Lucia Stănculeanu^1,2, Daniela-Luminiţa Zob¹

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

Vascular leiomyosarcoma, an extremely rare tumor, is characterized by aggressiveness and a high likelihood of local recurrence and metastasis. It tends to affect women more frequently and is included in the category of malignant soft tissue tumors, representing less than 1% of all malignant tumors in adults. We present the case of a 42-year-old female diagnosed with factor V Leiden mutation and a history of deep iliofemoral venous thrombosis. In February 2022, the patient was urgently admitted with chest pain and hemoptysis. Computed tomography (CT) revealed a massive bilateral pulmonary embolism (PE), with progression under heparin therapy, leading to the decision to implant an inferior vena cava filter. Further evaluation involved consultations with specialists in hematology, rheumatology, gastroenterology and general surgery, due to the various symptomatology, including persistent abdominal pain, which raised the suspicion of enteric ischemia. Computed tomography angiography (CTA) identified a possible tumorous lesion in the iliac veins, leading to an oncology consultation and biopsy, which confirmed the diagnosis of vascular leiomyosarcoma with secondary pulmonary metastases. The patient underwent six cycles of first-line chemotherapy with doxorubicin and ifosfamide. In September 2022, the imaging assessment indicated a stationary aspect of the disease, and the treatment with tyrosine kinase inhibitor was initiated, the patient currently having a very good performance status. In conclusion, due to its rarity and unusual clinical course, the diagnosis and treatment of vascular leiomyosarcoma present challenges for the multidisciplinary medical team.

Keywords: vascular leiomyosarcoma, factor V Leiden, doxorubicin, ifosfamide, tyrosine kinase inhibitor

 

Uncommon presentation of breast cancer recurrence unveils second primary lung cancer

 

Alina-Lavinia Grigore

“Elias” University Emergency Hospital, Bucharest, Romania

 

We present the case of a 54-year-old woman who underwent in 2009 radical surgery for left luminal B breast cancer, followed by adjuvant chemoradiotherapy. Thirteen years later, in July 2022, the patient presented as an emergency with severe acute abdominal pain and fever. A full body CT scan revealed pneumoperitoneum due to perforation of an ileal mass, a left pulmonary infiltrative mass, mediastinal and abdominal lymphadenopathy. An emergency segmental enterectomy was performed. The histological examination showed ileal metastasis of a triple-negative breast cancer, establishing the diagnosis of metastatic breast carcinoma. The case was discussed at the multidisciplinary board. Biopsy of the pulmonary mass along with additional testing were decided in the first place. The lung sample testing revealed the presence of a poorly differentiated NSCLC adenocarcinoma – ALK negative, EGFR negative, PD-L1<1%, confirming a second primary carcinoma. The tumor board decided the treatment initiation with paclitaxel, carboplatin, atezolizumab and bevacizumab for six cycles, followed by atezolizumab maintenance. At the moment, the patient is on atezolizumab, having registered a partial response. The highlights of the clinical case are the belated unusual recurrence of the breast cancer and the diagnosis of the second primary lung cancer. Moreover, the decision regarding the right treatment that fights both primary malignancies, while taking into consideration the cumulative toxicities and the available clinical protocols, was a challenging one. The patient’s response to treatment remains a matter of ongoing observation. It is anticipated that a decision regarding the subsequent line of therapy will be notably intricate.

Keywords: breast cancer recurrence, primary lung cancer, case presentation

 

Cytokine release syndrome – diagnosis and management

 

Mirela Haţegan

“Prof Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca; ARENSIA Exploratory Medicine, Bucharest, Romania

 

Cytokine release syndrome (CRS) is a heterogenous group of illnesses that can cause the scariest clinical scenarios for clinicians, patients and families. It is a hyperinflammatory disorder that can lead to multiple organ failure, requiring intensive care, having a high mortality. This is an expected side effect of CAR-T cell therapy, but lately it has been mentioned as a possible adverse event with the new drug development of immune check point inhibitors (CPI) in oncology. Symptoms can range from mild and flu-like to severe multiorgan system failure and death. CRS is triggered by the massive release of IFN-g by activated T cells or tumor cells, which in turn induces the activation of macrophages. The activated macrophages produce excessive amounts of IL-6, IL-8, IL-10 and TNF-a. Cytokine release syndrome typically presents with fever and temperatures frequently exceeding 40°C. More severe cases are characterized by hypotension and capillary leak, often leading to hypoxia and pulmonary edema. Organ dysfunction may occur secondary to hypotension or hypoxia, but may also result from the direct effect of cytokine release. One of the best ways of diagnosing CRS is by measuring IL-6, and this precedes the elevation of CRP with the caveat of limited access to a real-time result. One way of overcoming this is having access to fast result of IL-6 strip test which we have implemented in our clinic. CRP can be a surrogate biomarker, and elevation above 200 mg/L correlates with severe CRS with a specificity of 100%. The treatment management requires stratification by severity, including antipyretics, antihistamine for mild cases, corticotherapy, anti-IL-6 therapy like tocilizumab, and anti-IL-1 drugs like anakinra for severe cases.

Keywords: cytokine release syndrome, hyperinflammatory disorder, anti-IL-1, anti-IL-6

 

Nivolumab-induced interstitial pneumonitis in melanoma – overdiagnosing or prevention of immune-mediated reactions

 

Ruxandra Horomnea, Cristina Orlov

“Elias” University Emergency Hospital, Bucharest, Romania

 

The introduction of immune checkpoint inhibitors has revolutionized cancer treatment, but the main side effects of those drugs are represented by unpredictable immune-mediated toxicities which appear when autoreactive T-cells are activated aberrantly and cause inflammation in various organs, such as lung, liver and skin. Recognizing and taking decisions regarding discontinuing the treatment may be crucial. However, diagnosing interstitial pneumonitis post-nivolumab in melanoma can be a challenge. The next presentation shows the case of a young male, 28 years old, known with congenital melanocytic nevi and vitiligo, who presented himself in September 2022 in a plastic surgery clinic for the excision of a mass on the scalp. After the histopathologic exam, the diagnosis of focal ulcerative melanoma developed from a congenital melanocytic nevus, Breslow >4 mm, invasive in the reticular derma, Clark 4 stage – T4b, LVI, was established. The immunohistochemical tests confirmed the diagnosis, and the BRAF status was negative. The CT scan from October 2022 revealed pulmonary micronodules and mediastinal adenopathies in which case the oncologic commission’s decision was an urgent PET-CT. The result presented the pulmonary micronodules as inactive, but captured activity in a subcutaneous secondary determination located on the left side of the abdomen, followed shortly by excision of the lesion and biopsy, alongside multiple Spitz nevi with evolving characteristics. The histopathological exam confirmed the secondary determination diagnosis, BRAF was still negative, and the administration of nivolumab 1 mg/kg + ipilimumab 3 mg/kg began. At the end of the four administrations, there was performed a re-excision on the left parietal side of the scalp, with histopathological confirmation of local melanoma relapse at the site of the cutaneous flap. In January 2023, nivolumab 240 mg (Q2W) was started. However, the full CT scan from late January presented multiple pulmonary micronodules bilaterally distributed with a “tree-in-bud” aspect which raised the suspicion of infection in the clinical context presented by the patient who had interactions in the last month with people who suffered from intercurrent respiratory illnesses, or secondary determinations or a post-drug administration reaction. The only symptom was a dry cough, moderate in intensity, SaO₂ 98%, with no fever or night sweats. It was decided in the oncology commission to continue the nivolumab and perform regular CT scans. In March 2023, the control CT scan showed the relative stationary aspect of the pulmonary bilateral micronodules, associated with minimally progressive septal thickening, with stationary aspect of the pleural micronodules and of the mediastinal adenopathies and complete regression of the “tree-in-bud” micronodules. A pulmonary consult was solicited because of the persistent dry cough over three months, and a bronchoscopy was performed – the result revealed no microbial flora or cancer cells, but it was described an alveolitis predominantly with lymphocytes. In April 2023, the ImmunoTox forum was reached and the response given recommended bronchial biopsy in order to exclude the carcinomatosis lymphangitis and the continued evolution of the cancer. The patient was informed and chose to postpone the procedure. Nivolumab 240 mg (Q2W) is continued on the clinical benefit. The last CT performed showed the stationary aspect of the lung, with no new lesions in the thorax, but with hepatomegaly and splenomegaly, both in progression in comparison with the previous scans. The next CT scan is scheduled in September-October 2023. The case particularities include the development of melanoma from a congenital nevus, the questioning of the etiology of pulmonary micronodules even from the beginning of the diagnosis, the dry cough as the only symptom in an infectious epidemiological context presented by the patient, but without the possibility of excluding the immune-mediated reaction or the progression of the cancer, which included the collaboration between oncology, pneumology and the international ImmunoTox forum. Even though the nivolumab-induced interstitial pneumonitis has a low frequency of 1-3% and most cases have mild symptoms, we consider that immunotherapy in this case has shown obvious clinical benefit, but any symptom of immune-mediated adverse reactions should be well investigated.

Keywords: nivolumab, interstitial pneumonitis, malignant melanoma

 

The evolution of neoadjuvant treatment in rectal cancer – experience of the Oncology Clinic of the “Elias” University Emergency Hospital

 

Cristian Iaciu¹, Manuela Barna², Andrei Anghel², Ramona Ionescu², Ana Markos¹, Ilinca Ribac¹, Lavinia Grigore¹, Ioana Cojocaru¹, Daniela Stan¹, Raluca Bădulescu¹, Cristina Badic¹, Oana Popescu¹, Monica Boghici¹

1. Oncology Clinic, “Elias” University Emergency Hospital, Bucharest, Romania

2. Radiotherapy Department, “Elias” University Emergency Hospital, Bucharest, Romania

 

The treatment in locally advanced rectal cancers continues to evolve. Therefore, in the past years, patients have benefited from either neoadjuvant radiochemotherapy or total neoadjuvant therapy (TNT), the latter demonstrating improved control of systemic disease and becoming, according to guidelines, the standard treatment in carefully selected cases. Studies have shown a higher therapeutic response rate in patients receiving TNT; however, the overall surviving rate is contradictory. The choice of treatment is made on the basis of these results, but the toxicities that may occur with each therapeutic strategy are weighed against each other, and the possibility of overtreatment of certain patients is also discussed. We performed a retrospective study in which there were included patients with rectal cancer, eligible for neoadjuvant treatment, in the last three years, in the Oncology Clinic of the “Elias” University Emergency Hospital, Bucharest. The aim was to compare the therapeutic outcomes between the two treatment strategies, the overall survival, the progression-free survival and the time until progression. We also monitored the tolerance of patients in terms of toxicities for the two therapeutic approaches. We conclude that there is better therapeutic response in terms of total neoadjuvant therapy, but without large differences regarding the global survival and with variable toxicities.

Keywords: neoadjuvant treatment, rectal cancer, clinical experience

 

The path followed by a case of HER2-negative HR-positive breast cancer from the moment of diagnosis to the present time: clinical case

 

Laura Iovanovici

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

 

Breast cancer represents the most common type of malignancy among women and is the second leading cause of death through neoplasia. Breast cancer is a heterogeneous disease, therefore tumors with different biological features have different clinical outcomes and responses to therapy. The prognosis and treatment choices are based on the characterization of tumor growth factor, the receptor status – ER, PR and HER2 expression. In the following, we will discuss the clinical case of a 59-year-old female patient diagnosed with left invasive ductal carcinoma. Immunohistochemistry tests revealed ER, PR receptors positive and HER2 expression negative. The first CT scan didn’t show any distant metastasis. It was initiated neoadjuvant chemotherapy followed by conservatory surgery. Postmastectomy, it was pointed out residual tumor and positive lymph nodes, therefore the next steps of the therapeutic behavior were radiotherapy followed by adjuvant chemotherapy, which was continued with hormonotherapy. The patient’s clinical status deteriorated fast, and pain alongside walking disability set in. The imaging reassessment indicated disease progression through bone metastasis. It was initiated the treatment with CDK4/6 inhibitors associated with aromatase inhibitors. The therapeutic response was spectacular, proving the treatment efficiency in a very short time, without any reactions. The patient’s clinical status improved within a few months and currently she is still under treatment. In conclusion, we present the management of a HER2-negative HR-positive breast cancer case and the efficiency proved by CDK4/6 inhibitors associated with aromatase inhibitors for metastatic disease.

Keywords: HER2-negative HR-positive breast cancer, case presentation, clinical evolution

 

Is there a predictive value of gender for response in metastatic melanoma patients treated with immunotherapy?

 

Irene Koyada, Bernas Arnaud, Vlad Pop, Paul Danciu, Bristena-Octavia Tristan, Claudia Burz

“Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, Romania

 

Introduction. There is a growing awareness regarding gender influences on the response of cancer to immunotherapy that is reflected by an increasing number of studies in many cases of tumors, including melanoma. A new revolution was marked by immunotherapy in this setting, but neither predictive factors were identified in response, nor selection criteria for targeted therapy of immunotherapy. Materials and method. A retrospective study was initiated with the hypothesis of comparing the impact of gender for response in cancer patients diagnosed with metastatic melanoma. For the inclusion, the patients were selected independent of BRAF status, treated with the combination checkpoint inhibitor drugs PD-1 inhibitor/CTLA-4 inhibitor: nivolumab/ipilimumab. For each patient, at the inclusion, the performance status was assessed, along with the neutrophils/lymphocytes ratio, thrombocytes/neutrophils ratio, and the value of LDH. Every patient was evaluated after four cycles of double immunotherapy and then every three months during the maintenance treatment. Statistical analyses will be performed to evaluate if there exists a statistical gender difference in response to double immunotherapy. Conclusions. The limited number of patients is not sufficient to validate the hypothesis, and more studies must be conducted on a larger cohort of patients to affirm the predictive value of the clinical and biological markers.

Keywords: melanoma, immunotherapy, gender, LDH, leucocytes

 

Duodenal metastatic obstruction from urinary bladder carcinoma: a case report

 

Diana-Elena Lazăr¹, Anca Munteanu²

1. Department of Medical Oncology, “Sf. Ierarh Dr. Luca” Municipal Hospital, Oneşti, Romania

2. Department of Radiotherapy, Regional Institute of Oncology Iaşi, Romania

 

Introduction and objectives. Intestinal metasta­ses from bladder cancer are a rare metastatic site with an unfavorable prognosis. In this case report, we describe for the first time a case of isolated duodenal metastasis and lung metastases from bladder cancer, associated with intestinal obstruction, as the first sign of metastatic spread, which had been treated with surgery, chemotherapy and immunotherapy. Materials and method. A 77-year-old smoker man presented with a two-month history of epigastric pain, melena and weight loss, with a state suggestive of intestinal obstruction. Computed tomography (CT) of the thorax, abdomen and pelvis showed multiple lung metastases, a tissue mass in the fourth part of duodenum and in the right bladder wall, extending posteriorly, with dilation of the ipsilateral ureter. The patient underwent surgical resection of the duodenum and proximal jejunum, with pathological examination confirming a poorly differentiated urothelial carcinoma metastasis to the duodenum. The patient was staged as T4N0M1 bladder carcinoma and, after a multidisciplinary discussion of the case, the patient was subsequently treated with chemotherapy and immunotherapy. Results. The patient unfortunately developed renal failure and died five months later, after three cycles of immunotherapy. Conclusions. It is critical to correctly diagnose the histological variants of duodenal metastatic obstruction to predict a patient’s prognosis and to determine the optimal treatment.

Keywords: bladder carcinoma, case report, metastatic obstruction

 

Complete response in high-grade serous ovarian cancer: luck by chance or predictable chemosensitivity?

 

Radu Matei¹, Anca Stolojanu¹, Crina Siminiceanu¹, Elena Dumitrescu¹, Loredana Ciontea¹, Dana-Lucia Stănculeanu^1,2

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

Introduction. Ovarian cancer is an underlying cause of mortality among women. High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer and is responsible for a disproportionate share of the fatalities. Despite the grim outlook, tailored therapy alongside early diagnosis improve the prognostic outcome. Case presentation. We report the case of a 34-year-old female, with a personal history of minor thalassemia, who was diagnosed with bilateral high-grade serous ovarian cancer (HGSOC), stage FIGO IIIB, pT3b pNO pM0, hormone receptor-positive, BRCA1 mutation positive. The patient underwent radical surgery with comprehensive staging and debulking. After recovery, the primary therapy was initiated with paclitaxel/carboplatin alongside bevacizumab, summing a total of six series during the span of four months. Imagistic evaluation was performed, and complete response was confirmed. Maintenance therapy with olaparib and bevacizumab was subsequently instituted. After six months of maintenance therapy, an imagistic reevaluation was performed, confirming the complete remission, and maintenance therapy was further continued. The up-to-present fortunate evolution may take an unexpected turn as the patient is infected with Borrelia burgdorferi, a pathogen with pro-oncogenic potential and tumor heterogeneity promoter properties in gynecological neoplastic disease. Conclusions. This case further strengthens the premises regarding the positive response rate of HGSOC hormone receptor positive to platinum-based chemotherapy, the overall survival rate and the progression-free survival. This report aims to additionally present the limited data on Lyme disease in gynecological cancers.

Keywords: HGSOC, hormone positive, BRCA1, chemosensitivity, Borrelia burgdorferi

 

Results of surgical treatment in patients with lung cancer undergoing a cardiovascular prehabilitation program

 

Igor Maxim, Ion Burlacu, Serghei Guţu

“Nicolae Anestiadi” Surgery Department 1, “Nicolae Testemiţanu” State University of Medicine and Pharmacy, Chişinău; Institute of Emergency Medicine, Chişinău, Republic of Moldova

 

Introduction. Lung cancer is one of the most commonly encountered types of cancer, with the highest mortality rate. The coexistence of lung cancer and cardiovascular disorders is becoming increasingly common. Aim. An analysis of postoperative results in patients who underwent surgical treatment for lung cancer and were included in a cardiovascular prehabilitation program. Materials and method. A sample of 105 patients who underwent surgery for normocellular lung cancer at the Institute of Emergency Medicine Chişinău, between 2016 and 2022, were analyzed. All interventions were performed through an open approach: pneumonectomy (19), lobectomy (78), or bilobectomy (8). Out of the total number of patients, 68 (64.76%) in Group I had associated cardiovascular disorders, either one or multiple, in their medical history, while the other 37 (35.24%) in Group II did not have cardiovascular comorbidities, but they presented with diabetes mellitus (21) or chronic obstructive pulmonary disease (16). Results. According to the Clavien-Dindo classification, the following complications were recorded. Group I (n=57, 83.82%): grade I – 38; grade II – 8; grade III – 10; grade IV – 1; grade V – 11. In patients without cardiovascular pathologies (Group II; n=37, 100%), the following results were observed: grade I – 11; grade II – 14; grade III – 6; grade IV – 6; grade V – 0. Patients who were included in the prehabilitation program, as evidenced by the cardiologic monitoring, endovascular interventions and reconstructive arterial interventions, showed better functional outcomes. Conclusions. Patients with lung cancer and cardiovascular comorbidities who are candidates for major lung resections require meticulous cardiovascular prehabilitation, which can optimize the efficacy of surgical treatment, reduce the rate of postoperative complications, and improve the quality of life.

Keywords: lung cancer, lung resections, cardiovascular prehabilitation

 

Prognostic value of platelet-lymphocyte ratio, neutrophil-lymphocyte ratio, and monocyte-lymphocyte ratio in head and neck squamous cell carcinoma (HNSCC) – a retrospective single-center study

 

Camil-Ciprian Mireştean^1,2, Cosmin-Mihai Stan^2,3, Roxana-Irina Iancu^4,5, Dragoş-Petru-Teodor Iancu^4,6, Florinel Bădulescu¹

1. University of Medicine and Pharmacy of Craiova, Romania

2. CFR Clinical Hospital, Iaşi, Romania

3. Vâlcea County Emergency Hospital, Râmnicu Vâlcea, Romania

4. “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania

5. “Sf. Spiridon” County Clinical Hospital, Iaşi, Romania

6. Regional Institute of Oncology Iaşi, Romania

 

Introduction. The identification of some prognostic markers in head and neck cancers (HNC) is necessary for the stratification of the therapeutic approach, with benefits in increasing treatment response rates and limiting the toxic side effects of treatments. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) are currently validated as cheap and accessible biomarkers in different types of solid tumors. The purpose of the study was to evaluate the possible biomarker value of NLR, PLR and MLR recorded pre-treatment (radiotherapy/chemotherapy) for prognostic purposes in HNC. Materials and method. The study was carried on 190 patients with HNC included in the oncology record in the oncology outpatient clinic of the Craiova County Emergency Clinical Hospital starting from January 2002 and deceased until December 2022. Among them, 40 patients treated multimodally in the clinic were included in the study of Oncology at the Craiova County Emergency Clinical Hospital for which the pre-treatment values (chemotherapy/radiotherapy) of NLR, PLR and MLR could be calculated. Overall survival (OS) values were correlated with NLR, PLR and MLR. Results. Median values for NLR, PLR and MLR were 6.15 (1.24-69), 200.79 (61.3-1775) and 0.53 (0.12-5.5), respectively. In the study, the mean values for NLR, PLR and MLR of 2.88, 142.97 and 0.36, respectively, were obtained. The median OS in the study group was 11 months (1-120). Although a negative Pearson’s correlation, the relationship between our variables was only weak, with values R=.07, p=.67; R=.02, p=.31; R=07, p=.62 being related with NLR, PLR and MLR, respectively, correlated with overall survival (OS). The median values of NLR, PLR and MLR were calculated (1.53, 90.32 and 0.18, respectively) for HNC cases with pre-treatment values of NLR<2 and HNC cases with NLR values ≥6 (23.5, 232.78 and 0.79, respectively). Median OS for cases with NLR<2 and NLR≥6 were 17.4 and 13 months, respectively. Conclusions. The negative correlations of NLR, PLR and MLR with OS reported in the study are in accordance with the data reported in the literature for locally advanced recurrent and metastatic HNSCC cases. The comparative analysis of the data in the group with NLR<2 and NLR≥6 highlights an advantage of 4.4 months in median OS in favor of the group with low values of NLR. Being cheap and accessible, these markers could change the therapeutic approach even in centers with limited resources. The role of borderline NLR values as a prognostic factor in HNSCC must also be defined. PLR and MLR are less evaluated as biomarkers, but the study demonstrates their potential to be used as prognostic biomarkers. It remains to be clarified if their inclusion in multivariable models along with NLR would bring a benefit.

Keywords: platelet-lymphocyte ratio, neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, prognostic factors, head and neck cancer

 

An eye on the news – a case report

 

Mihaela Moraru¹, Iolanda Goga¹, Adriana-Monica Nichita¹, Enache Cioc¹, Maria-Andreea Ilie¹, Daniela-Luminiţa Zob¹,
Dana-Lucia Stănculeanu^1,2, Andreea Ionescu¹, Adelina-Silvana Gheorghe^1,2, Elena-Adriana Dumitrescu¹

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

Ocular melanoma is a rare and aggressive form of eye cancer, with limited treatment options. Tebentafusp is a breakthrough immunotherapy that has attracted attention for its unique approach to treating ocular melanoma. This abstract describes the compelling case of a woman previously treated for uveal melanoma with ocular brachytherapy who later presented with challenging liver metastases. After a two-year interval, she underwent a series of investigations, including a liver biopsy, which confirmed the presence of liver steatosis. Unfortunately, after a four-year interval, magnetic resonance imaging (MRI) and positron emission tomography (PET-CT) showed nodular liver lesions. Surgical intervention confirmed the liver metastasis, and within a remarkably short period of two months, the liver metastasis recurred. A positive HLA-A*02:01 test led to the decision to initiate systemic therapy with tebentafusp. The first five doses were administered in the intensive care unit, under close supervision. Despite side effects such as skin rashes and fever, neither cytokine release syndrome, nor prolongation of the QT interval occurred. After two months, the abdominal MRI showed the improvement of liver lesions and the PET-CT scan indicated no further lesions. In conclusion, the decision to initiate systemic therapy with tebentafusp resulted in positive outcomes, despite the possibility of severe side effects.

Keywords: uveal melanoma, brachytherapy, liver metastasis, positive HLA-A*02:01, tebentafusp

 

The role of pre-treatment inflammatory biomarkers in the prediction of response to cetuximab therapy in metastatic colorectal cancer

 

A. Necula^1,3, A. Belu², C.C. Burz^1,2

1. “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. “Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, Romania

3.  Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

 

Objectives. Targeted therapies have shown remarkable outcomes in disease control and survival for metastatic colorectal cancer (mCRC). Discerning the patients who stand to have a better treatment response remains a difficulty. Our retrospective single-center study aimed to evaluate the prognostic utility of inflammatory biomarkers when implementing FOLFOX/FOLFIRI chemothe­rapy plus anti-EGFR monoclonal antibodies (cetuximab) and to share our center’s experience. Materials and method. Out of 226 mCCR patients for which FOLFOX/FOLFIRI + cetuximab was initiated at our center between 2014 and 2023, 38 cases met the inclusion criteria: KRAS-wt status, three months of follow-up CT imaging, accessible histology, and availability of laboratory data. We focused on assessing the role of neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios, which were quantified prior to the commencement of the FOLFOX/FOLFIRI + cetuximab protocol. To evaluate the treatment response, we relied on follow-up CT conducted at the three-month mark. We used three distinct disease control (DC) criteria: remission (R), stable disease (SD), and progressive disease (PD). Additionally, we tested for any potential correlations between the tumor site, patients’ demographic variables and their treatment response. Results. We observed the lowest N/L ratio values in the R group, followed by progressively increasing values in the SD group and the PD group. Noteworthy was the presence of outlier values featuring elevated L/R ratios, associated only with the PD group (N/L>6). Conversely, in the context of the P/L ratio, a distinct upward trend from the R group to the PD group wasn’t as evident, however with lowest values corresponding to the R group. Left-sided tumors exhibited a more favorable treatment response, accounting for 80% of tumors in the R group and 85% in the SD group. Male patients demonstrated an improved treatment response, with 15% achieving remission compared to 11% in the female subgroup. We found no discernible correlation between patients’ age and treatment response (p=0.96). Conclusions. Inflammatory biomarkers hold value in managing systemic treatment for mCRC patients. A low N/L ratio corresponds to better response and remission, while higher values, especially exceeding N/L>6, correlate with progressive disease. Additionally, left-sided tumors exhibit a more favorable response to the FOLFOX/FOLFIRI + cetuximab scheme. These findings emphasize the utility of biomarker use in the therapeutic strategy, as seen in our center’s experience.

Keywords: inflammatory biomarkers, prediction of response, cetuximab

 

A case report of synchronous upper arm sarcoma and breast cancer

 

Adriana-Monica Nichita¹, Mihaela Moraru¹, Iolanda Goga¹, Enache Cioc¹, Andreea Ilie¹, Octav Ginghină^1,2, Mara Mardare¹,
Ariana-Ştefania Neicu¹, Adina-Elena Ene¹, Vlad Ştefănel¹, Alina-Oana Moldovan¹, Dana-Lucia Stănculeanu^1,2, Adelina-Silvana Gheorghe^1,2, Daniela-Luminiţa Zob²

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

Soft tissue sarcomas are rare tumors, accounting for less than 1% of all malignancies, while, on the contrary, breast cancer is the most common form of cancer among women. We selected the case of a 75-year-old woman presenting with a tumoral mass on the posterolateral side of the right upper arm. The MRI scan displayed a 7/4 cm lesion with no bone or muscle involvement, and the CT scan excluded lymph node involvement or distant metastasis. The histopathologic and immunohistochemical testing revealed a high-grade leiomyosarcoma diagnosis. While being evaluated for the sarcoma, another suspect lesion was discovered – a 4.5-cm mass in the lower outer quadrant of the left breast with no apparent axillary lymph node involvement. Leiomyosarcoma resection was performed together with breast tumor core needle biopsy, which revealed moderately differentiated invasive ductal carcinoma with negative hormonal receptors and positive HER2. The patient followed local upper arm radiotherapy and a neoadjuvant treatment scheme consisting of epirubicin and cyclophosphamide, followed by dual anti-HER2 therapy and platinum compound. Post-surgical assessment revealed no residual breast tumor, while the imaging studies showed no sign of upper arm recurrence and no sign of distant disease. The case highlights the importance of a thorough patient evaluation and the necessity of early detection of cancer, regardless of type or incidence, as it allows for better treatment responses and improved outcomes.

Keywords: synchronous neoplasia, sarcoma, breast cancer

 

Immune-related toxicity and its impact on oncological outcomes in patients with melanoma – experience of the Clinic of Medical Oncology from the “Elias” University Emergency Hospital

 

Cristina Orlov-Slavu, Andreea Pătraşcu, Ruxandra Horomnea, Ana Mihai, Răzvan Stoica, Andreea Scînteie, Alexandra Câţoiu, Alexandra Hoza

“Elias” University Emergency Hospital, Bucharest, Romania

 

The discovery and approval of immune therapy have brought considerable benefits in the management of some selected oncological disorders. In patients with advanced melanoma, the treatment with immune checkpoint inhibitors (ICIs) has changed the direction of the disease, offering improvements in the control of the disease and survival outcomes in some subgroups of patients. Despite promising results, immune-related adverse events (irAE) related to this kind of therapy are challenging issues, with life-threatening potential and the need for prompt and appropriate management. In the last few years, some studies focused on proving the hypothesis that the occurrence of immune-rela­ted adverse events leads to better survival outcomes in these patients, but the data are inconsistent and a conclusion hasn’t been extrapolated. We performed a retrospective study that included melanoma patients treated with ICIs in the last five years in the Clinic of Medical Oncology from the “Elias” University Emergency Hospital, Bucharest. Our work aims to present the most frequent immune-related adverse events and their management. In this study, we also analyzed the correlation between irAE occurrence and clinical outcomes, including progression-free survival, overall survival, duration of response, and control of the disease. We also wanted to find out if a correlation between the presence of irAEs and the survival outcomes can be established, if there was a correlation between the type of adverse events and the survival outcomes, and if steroid use was correlated with worse outcomes. Finally, we conclude that immune therapy has brought a remarkable benefit in survival for melanoma patients, but the toxicity related to this therapy can be challenging in some cases, especially in cases with promising survival outcomes.

Keywords: immune-related toxicity, malignant melanoma, “Elias” oncology clinic

 

Managing metastatic ovarian cancer: a case report with BRCA1 mutation

 

Mădălina-Raluca Ostafe

Victoria Hospital, Euroclinic Oncology Center, Iaşi, Romania

 

Introduction. Metastatic ovarian cancer represents a significant challenge in oncology due to its aggressive nature and therapeutic complexities. This case report provides insights into the experience of a 45-year-old female patient with metastatic ovarian cancer, revealing the details of her diagnosis, treatment, and outcomes. Patient considerations. The patient's journey started in March 2022, with the presence of lower abdominal pain leading to her hospitalization, where she went through a radical hysterectomy with bilateral oophorectomy. Imaging showed multiple secondary lesions in the lungs and lymph nodes, highlighting the severity of her condition. The surgical specimen was analyzed by pathologists, revealing a high-grade serous tubal carcinoma, while the subsequent genetic testing showed a positive BRCA1 mutation, signifying a genetic predisposition. Diagnosis. The patient was therefore diagnosed with stage IV ovarian cancer (pT2a-cN1 cM1pul,lym), characterized by a serous tubal carcinoma and BRCA1 positive mutation. Interventions. After the diagnosis, the patient underwent six cycles of platinum-based chemotherapy combined with targeted therapy (paclitaxel + carboplatin + bevacizumab), followed by maintenance targeted therapy, which incorporated a PARPi (olaparib), as indicated by her mutational status (BRCA1 positive). Outcomes and lessons. Following chemotherapy and maintenance targeted therapy, the subsequent imaging revealed a stable disease, highlighting the importance of patient-oriented interventions using genetic insights to guide treatment decisions.

Keywords: ovarian cancer, BRCA1 mutation, case presentation

 

Co-occurrence of melanoma and sarcoidosis in a patient – case report

 

Annamária Patka, Claudia Burz, Sergiu-Remus Lucaciu

“Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, Romania

 

Case presentation. This report details the case of a 35-year-old male patient who sought medical attention in June 2023 due to an irregular skin lesion on his right thigh. Following a clinical evaluation, the patient underwent surgery. A sentinel node biopsy confirmed lymph node metastasis of melanoma, and tumor DNA testing detected a mutation in the BRAF V600E gene. Consequently, the patient received a diagnosis of BRAF-positive malignant melanoma, classified as pT4bN1aL1Pn0R0. During the pre-therapeutic assessment, a CT scan was conducted, revealing multiple pulmonary micronodules with a centrolobular/diffuse distribution. Subsequently, bronchoalveolar lavage was performed, and the collected samples were sent for histopathological testing. The immunohistochemical staining for CD8 revealed the presence of lymphocytes, accounting for approximately 40% of the total cell population, alongside a small number of neutrophil and eosinophil polymorphonuclear cells. Notably, there were no indicative features of malignancy. Given the nonspecific nature of the CT scan results, a PET scan was performed. The PET scan did not definitively rule out the possibility of pulmonary and mediastinal sarcoidosis. To further investigate the case, the patient underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which revealed a non-necrotizing chronic granulomatous inflammatory reaction. Additional examinations unveiled elevated levels of calciuria (484.5 mg/24 h; upper limit of normal=320 mg/24 h) and increased angiotensin-converting enzyme levels. Discussion. Sarcoidosis is an inflammatory disease that can affect multiple organs in the body, most commonly the lungs and lymph nodes. It is characterized by the formation of granulomas (small clumps of immune cells) in the affected tissues. Sarcoidosis can mimic metastasis, especially in the mediastinum, which can pose a diagnostic challenge. Managing both conditions can be complex and requires a multidisciplinary medical approach.

Keywords: malignant melanoma, sarcoidosis, case report

 

Epigenetic and genetic alterations for early detection of pre-cancerous ovarian lesions

 

Laura A. Pop, Adriana I. Gaia-Oltean, Andreea-Mihaela Nuţu, Ioana Berindan-Neagoe

“Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

 

Introduction. Ovarian cancer is one of the most aggressive cancers worldwide, associated with a prior diagnosis of endometriosis in several cases. Our study correlated genetic and methylation profiles of ovarian endometrioid cancer compared to endometriosis patients, identifying common and specific patterns for these associated pathologies. Materials and method. We evaluated the genetic profile of 50 ovarian endometriosis and 20 ovarian endometrioid carcinoma tissue samples with next-generation sequencing using cancer panel and BRCA. In addition, the DNA methylation profile was evaluated for both cohorts of patients using the MLPA. Results. We observed several mutated genes that were common for both types of patients, but we also identified mutated genes that were characteristic for each group. Also, we identified genes that are highly methylated only in endometriosis samples (PYCARD, RARB, RB1, IL2, CFTR, CD44 and CDH13) and the MLH3 gene was methylated only in endometrioid ovarian carcinoma samples. BRCA1, CADM1, PAX6, and PAH genes are mainly methylated in endometrioid ovarian carcinoma patients. We identified a correlation for the cancer group between tumor stage, copy number alterations and the presence of metastases; the presence of BRCA1 pathogenic variants was correlated with tumor differentiation degree, TP53 variants and copy number aberrations. Conclusions. Similar pathways were altered in both endometriosis and ovarian endometrioid carcinoma, meaning that a diagnosis of endometriosis with a high methylated genes profile could be an early marker for a potential evolution to cancer. Also, the GATA2 and CREM hypomethylation and ATM hypermethylation, together with a higher degree of tumor differentiation or tumor stage are associated with a poor prognosis in patients with ovarian endometrioid carcinoma.

Keywords: epigenetic and genetic alterations, ovarian cancer, early detection

 

Importance of researching the resistance mechanisms in TKI therapies

 

Vlad-Vasile Pop, Bristena-Octavia Tertan, Claudia Burz

“Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, Romania

 

Introduction. Non-small cell lung carcinoma (NSCLC) represents a percentage of 80-90% of total lung cancers, with a change in the distribution of histology marked by the increase in the rate of adenocarcinoma and decrease in the rate of squamous cell carcinoma. Moreover, NSCLC tumorigenesis may be classified into two mechanisms, one of them being the oncogene-addicted pathway with the most frequent mutations harbored in the EGFR and KRAS proto-oncogenes. Case presentation. In 2018, a 74-year-old patient, known as a nonsmoker, with no exposure to toxins, was admitted to the “Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, after being diagnosed with a lung adenocarcinoma of the left lobe, stage IV (right lung, pleural and pericardial involvement, left breast, axillary, abdominally and peritoneal lymph nodes, left adrenal gland), PD-L1 negative, with EGFR and ALK mutations in work. The patient was WHO 2 on account of the aggravation of dyspnea despite the thoracocentesis. While the mutational panel was not finalized, after the exclusion of another left breast primary, chemotherapy with carboplatin/gemcitabine was initiated, with the amelioration of symptoms after one cycle. Due to the radiological partial response after three cycles, the regimen was continued for six cycles, but at the end of it, a progression disease by peritoneal involvement was objectified on the CT scan. Having the notion of an EGFR mutation, a targeted therapy by erlotinib was initiated, with a partial response for seven months, until the aggravation of the respiratory symptoms and a new multisite progression. As a consequence of the rapid change of the ECOG status from 1 to 2, a liquid biopsy was performed (patient not fit for a tissue biopsy) and a new third line was initiated with Taxotere®, because of the urgency of quick amelioration of symptomatology. Unfortunately, neither a significant clinical benefit, nor a radiological response was achieved, but the liquid sample proved the presence of T790M mutation in the exon 20 which permitted the initiation of osimertinib in the fourth line, with a remarkably clinical response and a radiological amelioration at third cycles. After seven months of treatment, she was admitted to the neurology department with the diagnosis of stroke due to a cerebral multisite progression. Not being eligible for surgery or stereotactic radiotherapy, whole-brain radiotherapy was conducted. Conclusions. This classical case perfectly exemplifies the importance of being aware – from the moment of diagnosis – of the mechanisms involved in oncogenesis, and the concomitant existence of resistance mechanisms to TKIs and their method of detection by liquid/tissue biopsy. This emphasizes the need to have reliable, easy and rapid methods and protocols to detect the possible oncogenes by PCR and NGS to help choosing the most efficient therapy. Regarding the resistance mechanisms and their occurrence, until nowadays we still do not know which one of them – liquid versus tissue biopsies – should be performed, due to the absence of comparison between the methods. Research in this domain must be continued and improved.

Keywords: lung cancer, EGFR, resistance, liquid biopsy

 

Clinical case: metastatic acral melanoma with c-KIT mutation

 

Sandra-Roxana Popa

“Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania

 

Acral melanoma is a rare subtype of melanoma (accounting for only 1-3% of all cases diagnosed) which is not believed to be caused by sun exposure and, therefore, it is located in areas that are not typically exposed to the sun, such as palms of the hands, soles of the feet or nail-beds. The prognosis is poorer when compared to other types of melanomas, for various reasons (distinct epidemiological and mutational profiles; unlike the other types, acral melanoma often goes undetected until it has reached an advanced stage). I present the case of a 54-year-old male patient diagnosed with plantar acral melanoma in September 2021 after noticing a 4-cm ulcerated tumor. After resection, it was confirmed to be a pT4b LV0 Pn1 R1, c-KIT mutated, BRAF-negative melanoma. Unfortunately, the patient presented in the oncology department only in April 2022, when, after clinical and imagistic examination, it was staged as pT4b N0 M1a, presenting inguinal and popliteal lymph node metastases. He underwent multiple systemic therapy lines, starting with immunotherapy doublet ipilimumab/nivolumab, followed by imatinib at progression, and he is currently following the third-line chemotherapy protocol with dacarbazine.

Keywords: malignant melanoma, c-KIT mutation, metastasis

 

Bioactivity of fucoxanthin alone and in combination on glioblastoma cell lines

 

Lavinia-Lorena Pruteanu

Department of Chemistry and Biology, Faculty of Sciences, Technical University of Cluj-Napoca, Baia Mare, Romania; Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

 

Glioblastoma is one of the most aggressive types of cancer, with a 14-month survival prognosis in 95% of cases following diagnosis and known treatment. The biological properties of algal lipids and novel biosynthetic enzymes from brown algae and marine bacteria are of increasing interest. The aim of this work was to elucidate the bioactivity of fucoxanthin alone and in combination with the prototypic PI3K inhibitor LY294002 and its modulation of gene expression via transcriptomics analysis in glioblastoma U87 MG cells, followed by pathway analysis. A combinatorial synergy in growth arrest between the two compounds, which can in part be predicted by the divergence in their drug-induced gene expression signatures, has been shown. By coupling gene expression analysis to signaling pathway analysis, the results reveal clearly differentiated effects of the two target compounds.

Keywords: fucoxanthin, glioblastoma cell lines, bioactivity

 

MiR-708-5p exerts a potential therapeutic role in NSCLC male patients due to its involvement in transcription factor modulations

 

Lajos Raduly¹, Cecilia Bica¹, Ovidiu Farc², Liviuţa Budisan¹, Cristina Ciocan¹, Antonia Haranguş³, Mărioara Simon³, Cornelia Braicu¹, Ioana Berindan-Neagoe¹

1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. Immunology Department, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania.

3. Bronchology Department, “Leon Daniello” Clinical Hospital of Pneumophthisiology, Cluj-Napoca, Romania

 

Non‐small cell lung cancer (NSCLC) comprises 85% of lung cancers. NSCLC has a high incidence and mortality. The present study aimed to investigate the role of miR-28-5p and miR-708-5p and to analyze the relationship between target coding genes and their signaling pathways. The two miRs were overexpressed in a patient cohort of 32 matched paired tumor and adjacent nontumoral tissue. All biological samples were collected from stage III and IV NSCLC patients. Due to the paralog structure of the two miRNAs, we conducted the study specifically on miR-708-5p, which showed a statistical significance between tumor tissue and adjacent nontumoral tissue. MiR-28-5p also revealed a significant difference, but at a lower level. We showed the critical roles of miR-28-5p and miR-708-5p in regulating ECM-receptor interaction, adherent’s junctions and Hippo signaling in the progression of NSCLC. Additional confirmation of the overexpression of miR-708-5p was done in the male TCGA patient cohort. The analysis using the Trans-Mir program revealed that the following transcriptional factors (TFs) may control miR-708: AR, ESR1, CREBBP, EOMES, EZH2, SOX2, TCF3/4, USF2; EZH2, JMJD1c, KDM2D, CXXC1, CXXC2, SFPQ, and MED1. These processes can be interrelated, particularly during the execution of the cell cycle. To analyze these connections, we performed a bioinformatics analysis of the correlation between TFs, based on genetic interactions, co-localization, physical interactions, co-expression and common pathways. We excluded predicted correlations and common protein domains.

Keywords: miR-28-5p, miR-708-5p, transcription factor, NSCLC

 

Is it stationary disease or progression?

 

Andreea-Daniela Scînteie

“Elias” University Emergency Hospital, Bucharest, Romania

 

A 70-year-old female patient, known with high-grade G3 right serous ovarian carcinoma, operated, pT1a pN0 FIGO IA, polychemotherapy and hormone-treated, BRCA without mutation, came to the emergency room for absence of bowel movement for four days and abdominal pain in the lower abdominal floor. She followed treatment with paclitaxel and carboplatin and local radiotherapy, with a favorable response. Subsequently, CA-125 increasing, the same treatment continued, with progression through M1LYM. She enrolled in the Athena trial. At progression, paclitaxel and carboplatin were withheld, but hypersensitivity reaction to carboplatin occurred. At the next treatment, she presented hypersensitivity reaction to paclitaxel. The line was changed to gemcitabine and carboplatin with desensitization, but the reaction to carboplatin reappeared. New progression by M1LYM was found. BRCA was retested, with mutation present. Liposomal doxorubicin in combination with bevacizumab versus olaparib was considered, but taking into account the possible progression under PARP inhibitors, the former was chosen. Under bevacizumab, the patient developed uncontrolled hypertension. At the current presentation, the abdominal ultrasound showed evidence of ascites fluid, in medium quantity. Due to high creatinine levels, native abdominal and pelvic CT scan were performed, which concluded stationary disease. Although imaging-wise the disease is stationary, the patient’s clinical presentation indicates further progression. Is there progression or not in this case?

Keywords: progressive disease, stationary disease, diagnostic

 

Combined anti-PD-1 and anti-CTLA-4 treatment in stage IV melanoma patients: bicentric analysis of real-world data

 

Alexandru-Dorin-Adrian Silaşi^1,2, Anna Carolin Sievert¹, Paul Danciu³, Adrian-Vlad Lefter^4,5, Vlad-Adrian Afrasanie^4,5, Daniel Sur^1,3

1. “Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. Department of Oncology, Bistriţa County Emergency Clinical Hospital, Bistriţa, Romania

3. “Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, Romania

4. “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania

5. Regional Institute of Oncology Iaşi, Romania

 

Background. This retrospective study evaluates stage IV melanoma patients treated with nivolumab and ipilimumab combination therapy with regards to survival data, incidence and severity of side effects, based on real-world data collected from the “Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, and the Regional Institute of Oncology Iaşi, Romania, between 2019 and the end of 2022. Methodology. The data were analyzed in SAS for Windows V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on overall survival (OS) and progression-free survival (PFS) were investigated with Cox regression. Results. Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI; 150-NA) and a median PFS of 211 days (95% CI; 113-430). Moreover, 45.3% of the patients experienced adverse events during the nivolumab + ipilimumab treatment, with some of them having multiple organ systems involved. Discussion. The OS values were lower than those reported in approval clinical trials, as the patients included in these trials are highly selected and most of them also include stage III patients, who have a significantly better prognostic than stage IV patients. But these results show a marked improvement when comparing to chemotherapy regimens previously used in these scenarios, before the introduction of novel agents.  Conclusions. This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

Keywords: immunotherapy combination, malignant melanoma, real-world data

 

Managing malignant pleural effusion – a challenging case of metastatic lung cancer

 

Crina-Maria Siminiceanu¹, Elena-Adriana Dumitrescu^1,2, Adelina-Silvana Gheorghe^1,2, Mihai Bălaşa¹, Lidia-Anca Kajanto¹,
Loredana-Maria Ciontea¹, Anca-Alexandra Stolojanu¹, Radu Matei¹, Sânziana Prundianu¹, Dana-Lucia Stănculeanu^1,2

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

Malignant pleural effusion (MPE) is a frequent complication in lung carcinoma, especially in adenocarcinoma. In this case report, we present the case of a 62-year-old male diagnosed with metastatic NSCLC, who underwent corpectomy of tumoral L4 vertebrae with implantation of titan cages for cauda equina syndrome. The initial imagistic evaluation showed a right pulmonary mass with multiple pulmonary metastasis, bone metastasis and minimum right pleural effusion, measuring 3 mm. The patient experienced chronic symptoms: right chest pain, shortness of breath while laying down, and coughs with gradual increase. Chest CT showed a right-sided massive pleural effusion and complete lung atelectasis with mass effect, resulting in mediastinal shift to the left side. Emergency thoracocentesis was performed and the cytology confirmed the malignant pleural effusion, but with Staphylococcus aureus suprainfection (MRSA). Aggressive antibiotic therapy was initiated and regular chest X-rays were done, with a partial expansion of the lung and a minimal regression of the pleural effusion, known as trapped lung syndrome. Further, an indwelling pleural catheter was required, with a moderate regression of the pleural effusion, subsequently improving the general condition of the patient. MPE is present in approximatively 15% of lung cancer patients at diagnosis, and thoracocentesis is the investigation needed for confirmation. This case report highlights the complexities of malignant pleural effusion, the therapeutic approaches and the importance of personalized therapy for a better outcome.

Keywords: malignant pleural effusion, lung adenocarcinoma, thoracocentesis, indwelling pleural catheter, trapped lung

 

Lung cancer and type 2 diabetes experience in Dolj County (southwest part of Romania) – a clinical, bioclinical and pathological study

 

Mihai-Cosmin Stan¹, Ciprian-Camil Mireştean², Daniel Stoica¹, Carmen-Florina Popescu³, Florinel Bădulescu⁴

1. Medical Oncology Department, Vâlcea County Emergency Hospital, Râmnicu Vâlcea, Romania

2. Department of Surgery, CFR Clinical Hospital, Iaşi, Romania

3. Department of Pathology, County Emergency Clinical Hospital Craiova, Romania

4. Oncology and Radiotherapy Department, University of Medicine and Pharmacy of Craiova, Romania

 

Introduction. Type 2 diabetes and cancer are the most important public health problems nowadays, and the mechanisms between the presence of diabetes and the development of malignancies remain unclear. The leading cause of cancer death in 2020 is attributed to lung cancer. This study aimed to highlight the impact of the association of these two diseases and the predominant histopathological type of lung cancer in the selected group, the glycemic imbalance, and information about the course and outlook for these patients. Materials and method. The authors proposed a case-control 10-year period study, between 2007 and 2017, of two groups of patients diagnosed with type 2 diabetes and lung cancer who underwent hospitalization in the Medical Clinic of Oncology of the Craiova Clinical District Hospital (ECCHC). Results. Our study showed a higher incidence of lung adenocarcinoma in patients diagnosed with type 2 diabetes. The inflammatory syndrome is more pronounced in the diabetic group, which is supported by correlations between lactate dehydrogenase (LDH), albumin and hemoglobin levels. The duration of cancer treatment in lung cancer and the survival rate are strongly influenced by the presence of diabetes as a concomitant disease.

Keywords: lung cancer, diabetes, inflammation, survival rate

 

An overview of safety profile and clinical impact of CDK4/6 inhibitors in breast cancer – a systematic review of randomized phase II and III clinical trials

 

Ioana-Miruna Stanciu, Andreea Parosanu, Cornelia Niţipir

“Elias” University Emergency Hospital, Bucharest, Romania

 

Introduction. Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer over the last decade. These inhibitors are currently established as first- and second-line systemic treatment choices for both endocrine-sensitive and endocrine-resistant breast cancer populations, alongside endocrine therapy (ET) or monotherapy. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. Although these drugs have been demonstrated to prolong overall survival (as well as progression-free survival in breast cancer patients), changing the paradigm of all current knowledge, they also cause important adverse events. This review provides the latest summary and update on the safety profile of the three CDK4/6 inhibitors, as it appears from all major phase II and III randomized clinical trials, regarding palbociclib, ribociclib and abemaciclib, including the most relevant 15 clinical trials. Aim and objectives. The greatest challenge in the research and development of CDK4/6 inhibitors might lie in dealing with the adverse effects and potential drug tolerance. Further, understanding the underlying mechanism and exploring the ideal combination therapy might help overcome the selectivity and drug tolerance of CDK inhibitors. Considering the similar efficacies and indications of palbociclib, ribociclib and abemaciclib, the evaluation of their toxicity profiles may facilitate treatment choice. This review explores the safety profiles of palbociclib, ribociclib and abemaciclib in all randomized phase II and III clinical trials. Materials and method. This systematic review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Extended systematic research was performed on ClinicalTrials.gov database clinical trials registries with results published or registered before July 2023. The keywords used were: palbociclib, ribociclib, abemaciclib, phase II and III, randomized, and available results. The last search was performed on the 8^th of August 2023. The search returned 690 results. Literature articles were systematically assessed by searching in the PubMed Medline database from January 2016 until July 2023. The following keywords were used: CDK4/6 inhibitors, breast cancer, and toxicities. The inclusion criteria were: clinical studies on breast cancer patients, clinical phase II and III studies using currently approved doses for palbociclib (125 mg/day orally for three weeks, followed by one week off), ribociclib (200 mg X 3/day orally for three weeks, followed by one week off) or abemaciclib (150 mg X 2/day orally in combination with ET or 200 mg/day orally in monotherapy), and studies for which safety data or at least one adverse reaction were reported in the article in the form of the percentage or number of patients. Only free full-text articles were assessed. The exclusion criteria were: articles with unavailable abstracts, non-English written articles, conference presentations, meta-analyses and literature reviews, non-clinical studies, post-hoc or subgroup analyses, retrospective studies, and studies in which the adverse effects were not reported. In vivo and in vitro studies were also excluded. The search returned 130 results, all of which were already included in the first search on ClinicalTrials.gov. Conclusions. CDK4/6 inhibitors are generally well tolerated. The most common adverse reactions encountered on CDK4/6 inhibitors treatment include neutropenia, leukopenia, anemia, thrombocytopenia, fatigue, gastrointestinal side effects, hepatotoxicity and QTc prolongation. However, there are some distinctions between palbociclib, ribociclib and abemaciclib. The most prevalent adverse effect of palbociclib and ribociclib is neutropenia, while particular for ribociclib are the QTc prolongation and hepatobiliary toxicity, and for abemaciclib, the gastrointestinal toxicity. All these adverse reactions can be very well managed due to the possibility of multiple dosage decreases and adjustments. Therefore, in clinical practice, acknowledging a side effect is of paramount importance to best manage it. To the best of our knowledge, this is the latest and newest literature review compounding all phase II and III randomized clinical trials regarding the three CDK4/6 inhibitors’ toxicities. This review will hopefully be of real help to all clinicians in managing the adverse effects of CDK4/6 inhibitors, by providing an easier way to research the reported percentage of specific adverse reactions in consecrated clinical trials.

Keywords: CDK4/6, breast cancer, overview

 

Impressive response on pembrolizumab monotherapy in a patient with metastatic NSCLC and multiple comorbidities: case report

 

Anca-Alexandra Stolojanu¹, Elena-Adriana Dumitrescu^1,2, Crina-Maria Siminiceanu¹, Adelina-Silvana Gheorghe^1,2, Loredana-Maria Ciontea¹, Matei Radu¹, Irina-Alexandra Chirea¹, Mihai Bălaşa¹, Raluca-Ioana Mihăilă¹, Lidia-Anca Kajanto¹, Dana-Lucia Stănculeanu^1,2

1. “Prof Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

We present a case of a successful pembrolizumab monotherapy in a patient with metastatic non-squamous NSCLC (non-small cell lung carcinoma) and multiple comorbidities. The clinical treatment is challenging for elderly patients with lung cancer who cannot tolerate chemotherapy and do not have cancer driver genes. Evidence-based medicine supporting the use of immunotherapy for patients with ECOG PS≥2 is lacking, but this treatment option can be considered based on the PEPS2 trial. We report the case of a 72-year-old male patient diagnosed with metastatic lung adenocarcinoma after a transbronchial lung biopsy. The first imagistic evaluation disclosed hilar/mediastinal lymphadenopathy and proximal femur metastases. The patient was staged as pT4N3M1. He had a history of mixed ventilatory defect, congestive heart failure, bilateral pleural effusion and giant inguinal hernia. The immunohistochemistry results from the primary lung lesion were negative for EGFR and ALK. The PD-L1 expression level was 90% positive in the primary lung lesions (HIGH PDL-1). We determined that the patient was in a poor condition (ECOG PS 2), at risk for many complications and difficulties in tolerating chemotherapy. We administered pembrolizumab monotherapy at a dose of 200 mg every three weeks (26 cycles). For the first evaluation of efficacy, the next imagistic scan was done after nine cycles of treatment and exhibited an impressive response: dimensional regression of tumoral mass and hilar/mediastinal lymph nodes slightly smaller. In addition, the ECOG status improved and the patient achieved stable disease on the long term without obvious immune-related toxicity. In conclusion, this case illustrates the successful use of pembrolizumab as a first-line treatment in a 72-year-old patient with lung adenocarcinoma. Considering the need to balance the survival benefits with the quality of life and acknowledging that elderly patients show poor tolerance to chemotherapy, older patients without driving genes should be offered immune therapies when possible.

Keywords: metastatic lung adenocarcinoma, immunotherapy, multiple comorbidities, pembrolizumab, monotherapy

 

Testicular neoplasm in a patient with growing teratoma syndrome? Case presentation

 

Monica Şerbulescu

Oncohelp Timişoara, Romania

 

Growing teratoma syndrome (GTS) is an uncommon clinical condition that presents with enlarging teratoma masses of the retroperitoneum or other locations. This enlargement typically occurs during or after systemic chemotherapy as part of the treatment for nonseminomatous germ cell tumors (NSGCT) of the testes, with normalized tumor markers. In our case, a 29-year-old man underwent right orchiectomy and four cycles of bleomycin, etoposide and platinum chemotherapy for T2 mixed NSGCT (40% teratoma, 40% choriocarcinoma and 20% seminoma). After chemotherapy, the assessment through a computed tomography scan revealed the appearance of new, subcentimeter lung nodules and the existing pulmonary nodular lesions with different behaviors, one showing significant growth (RUL), while the other has decreased significantly (LLL), along with a decrease in the size of retroperitoneal lymph nodes. His alpha-fetoprotein was 3.34 ng/ml, lactate dehydrogenase was 285.75 U/I, and beta subunit of human chorionic gonadotropin was 0.28 m UI/ml. According to the medical literature, the treatment is surgical. Thus, the patient was referred to the thoracic surgery department for the excision of the remaining tumors, and at present we are waiting for the histological findings.

Keywords: lesions growing under chemotherapy, testicular neoplasm, growing teratoma syndrome

 

PEComa with TFE3 mutations – from identification to treatment

 

Oana Ştefan, Simona Iacob 

Pathology Department, Personal Genetics, Bucharest, Romania

 

The perivascular epithelioid cell tumor (PEComa) is a rare entity in oncologic pathology. Our presentation focuses on the analysis of a clinical case of PEComa with an immunophenotype suggestive of the presence of TFE3 mutations, highlighting the diagnostic aspects, pathogenesis, and treatment modalities of this case. We present the case of a 53-year-old female patient with a history of breast neoplasm, who was found to have an intravesical polypoid formation attached by a stalk to the posterior wall of the urinary bladder, at the midline, during a computed tomography scan as part of her oncologic assessment. Following histopathological and immunohistochemical examination, the final diagnosis of extrarenal PEComa with uncertain biologic potential, with morphology and immunophenotype suggestive of the presence of TFE3 rearrangements, was established. The prognosis for these tumors can vary and depends on factors such as tumor size, location and extent. The treatment typically involves surgery when feasible. In some cases, targeted therapies such as mTOR inhibitors may be considered. In conclusion, TFE3 rearranged PEComas represents a rare category of tumors that require specialized diagnostic techniques and a multidisciplinary approach for the therapeutic management.

Keywords: perivascular epithelioid cell tumor, TFE3 mutations, treatment indications

 

Nivolumab-induced adrenal insufficiency in a metastatic melanoma patient – case report

 

Anda-Ştefania Trandafir¹, Elena Şerban¹, Laurenţia-Nicoleta Galeş^1,2

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania

2. “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

This case report aims to present the importance of diagnosing adrenal insufficiency and treating it at an early stage to prevent severe outcomes that may result in the discontinuation of effective anticancer therapy or even in patient’s death. A 48-year-old female patient, hypertensive, without any other pathological history, was admitted in the oncology clinic for a pigmented tumor at the left leg, affirmative in evolution for several years, with ulceration and bleeding in the last months. The clinical examination revealed an exophytic pigmented, ulcerated, bleeding tumoral formation of 2.5/3 cm in diameter and with a vertical growth of 1.5 cm, situated on the posteroinferior left calf, without superficial palpable adenopathies, otherwise the clinical examination being within normal limits. The blood tests were within normal limits. Excisional biopsy was performed (September 2018), after which the malignant nodular melanoma Clarck III, Breslow>4 mm with free excision edges (pT4bpNx), was decelated. The imaging investigations performed with pelvic, head, thorax and abdomen CT and ultrasound (for lymph nodes) excluded the presence of regional secondary determinations or distant metastases. Following the lymphoscintigraphy, performed later, pericicatricial lymphatic drainage was revealed in the left inguinal region, and sentinel lymph nodes were excised. The histopathological examination (December 2018) revealed massive metastasis of malignant melanoma, so the TNM staging was T4bN1M0. Adjuvant treatment with interferon was initiated (May 2019) with further evolution of M1SKI (inoperable metastasis in the proximal third of the thigh in June 2019). Immunotherapy with ipilimumab 3 mg/kg b.w. and nivolumab 1 mg/kg b.w. was initiated (June 2019), followed by maintenance treatment with nivolumab 240 mg every two weeks, considering that it was well tolerated, then nivolumab 480 mg every four weeks. After one month under immunotherapy, the patient developed endocrine disorders with subclinical hyperthyroidism (TSH 0.013 microIU/ml, FT4 within normal limits) remitted under treatment with Thyrozol®. Two months after the immunotherapy initiation, the patient complained of extreme fatigue, nausea and inappetence, starting seven days prior. Blood pressure was 105/60 mmHg. Serum cortisol was <1 nmol/L, which is why the patient was investigated from an endocrinological point of view. Following the investigations, the diagnosis of adrenal insufficiency was established and long-term substitution treatment with prednisone 2 mg/kg b.w. was initiated, gradually reduced to prednisone 10 mg maintenance dose. Nivolumab was initially stopped and reinitiated when prednisone dosage reached 10 mg. Under immunotherapy, the patient had a favorable oncological outcome, without local relapses or distant metastases at the imaging evaluations performed periodically. The patient in this case has experienced common manifestations of adrenal insufficiency, which is one of the rare adverse events associated with ICI that occur in less than 1% of patients. Given the nonspecific manifestations, it can be easily overlooked if adverse events of immunotherapy are not suspected. Although rare, adrenal insufficiency is a life-threatening side effect of immune checkpoint inhibitor drugs that should be recognized immediately and managed with glucocorticoids.

Keywords: metastatic melanoma, immunotherapy, nivolumab, endocrine disorders, adrenal insufficiency

 

Incidental discovery of colonic metastasis in a stage IV breast cancer

 

Nicoleta-Andreea Tudose

Colţea Clinical Hospital, Bucharest, Romania

 

We are going to discuss the clinical case of a 66-year-old woman, with a history of controlled type 2 diabetes and hypertension. In March 2022, she underwent mammography, revealing a BIRADS 5 lesion in the right breast and a suspicious right axillary lymph node with biopsy indication. The histologic examination confirmed the diagnosis of luminal B HER2-negative NST breast cancer. Further investigations confirmed the diagnosis of stage IV breast cancer with peritoneal metastases. The treatment with abemaciclib was initiated in May 2022, but it was poorly tolerated and resulted in persistent grade 3 diarrhea, that required switching to palbociclib, which was better tolerated. TAP CT scan from September 2022 displayed a partial response, with the resolution of peritoneal metastases. In April 2023, she was enrolled in a screening program for occult bleeding, which resulted in a positive FIT test and a further recommendation for colonoscopy. The colonoscopy examination was incomplete due to severely congested erythematous mucosa, and multiple biopsies were obtained from the rectum, ascending and transverse colon which revealed metastasis of the same histology as breast carcinoma in the ascending colon. In conclusion, we had a partial response to CDK4/6 treatment in metastatic breast cancer with peritoneal metastases from the onset and an incidental discovery of colonic metastasis after a positive FIT test in an asymptomatic patient with no gastrointestinal symptoms and no suggestive CT scan of preexisting colonic metastasis or progressive disease at this level.

Keywords: colon metastasis, breast cancer, case presentation

 

Synchronous bilateral breast cancer: case report

 

Corina Vieru

Colţea Clinical Hospital, Bucharest, Romania

 

Synchronous bilateral breast cancer is a rare presentation of breast cancer, accounting for 1-3% of all breast cancer cases. We present the case of a 43-year-old premenopausal woman who, in October 2021, had at the initial evaluation suspicious bilateral breast and axillary lesions that required an MRI examination, being classified as BIRADS 4C on the right side, respectively BIRADS 5 on the left side. After biopsy, a CT scan was performed and the patient was diagnosed with right breast cancer, stage IIB (cT2 cN1), luminal A, and left breast cancer stage IIB (cT1 cN2), luminal B – HER2 positive. Bringing together the therapeutic options specific to each phenotype, the regimen chosen as neoadjuvant systemic treatment was, according to the NCCN guidelines version 2.2022, docetaxel/carboplatin/trastuzumab/pertuzumab administered every three weeks, for a total of 4-6 cycles. The therapeutic efficiency was monitored after four cycles of treatment, announcing stable disease for right breast lesions, respectively significant size reduction of the left tumor, without axillary lymph nodes. The patient was referred to the general surgery service for serial surgical interventions, right radical mastectomy being the one performed initially – ypT1b ypN0, luminal A; later, on the left side – ypT2(m) ypN0, luminal A. The patient completed the adjuvant treatment composed of radiotherapy, hormonal therapy and trastuzumab-emtansine. In this case, we mention the challenge of a synchronous bilateral breast cancer, with different phenotypes, which needed the correct therapeutic option, and allowed us to ask questions related to the incidence and prognostic impact of HER2-positivity loss.

Keywords: synchronous bilateral breast cancer, different phenotypes, treatment

 

Genomic and transcriptomic profile in malignant melanoma patients

 

Oana Zănoagă¹, Cornelia Braicu¹, Laura Pop¹, Cristina Ciocan¹, Cecilia Bica¹, Rareş Buiga², Radu Pîrlog^1,3, Lajos Raduly¹, Simona Gurzu⁴, Ioana Berindan-Neagoe¹

1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

2. “Prof. Dr. Ion Chiricuţă” Institute of Oncology, Cluj-Napoca, Romania

3. Pathology Department, County Emergency Clinical Hospital Cluj-Napoca, Romania

4. “George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology, Târgu-Mureş, Romania

 

Malignant melanoma continues to remain one of the most aggressive malignancies worldwide and, despite significant advances in immunotherapy and targeted strategies, the mortality rate is increasing. The aim of our study was to understand the mechanisms involved in the development of malignant melanoma in patients with primary tumors locally advanced with pathological status pIIIb and pIVb, using expression profiling of miRNAs through microarray analysis, mutational status and frequency among patients. NGS cancer panels and the usual IHC staining performed in the clinic were used. MiR-205, miR-122, miR-192, miR-125b, miR-21-5p, miR-210, miR-29c, miR-221, miR-143-3p, let-7c and let-7b are a few relevant miRNAs identified in our study to be involved in targeting major genes in malignant melanoma. Moreover, our data demonstrated that S-100 remains the most suitable marker for melanocytic lesions among IHC markers, and that HMB-45, Melan-A and MITF exhibited a sensitive specificity, together with S100. Our results revealed a specific profile between males and females in both molecular analyses. Furthermore, we demonstrated that the actual biomarkers used for immunohistochemistry staining are not specific enough to offer a complete overview of the tumor status. Therefore, we propose the evaluation of several miRNAs’ candidates in larger patient cohorts and in correlation with the mutational status of melanomas in males and females, separately.

Keywords: malignant melanoma, genomic profile, transcriptomic profile