Background/Objectives: Immunotherapy has changed the therapeutic approach for various solid tumors, especially lung tumors, malignant melanoma, renal and urogenital carcinomas, demonstrating significant antitumor activity, with tolerable safety profiles and durable responses. However, not all patients benefit from immunotherapy, underscoring the need for predictive biomarkers that can identify those most likely to respond to treatment. Methods: The integration of predictive biomarkers into clinical practice for immune checkpoint inhibitors (ICI) holds great promise for personalized cancer treatment. Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), microsatellite instability (MSI), gene expression profiles and circulating tumor DNA (ctDNA) have shown potential in predicting ICI responses across various cancers. Results: Challenges such as standardization, validation, regulatory approval, and cost-effectiveness must be addressed to realize their full potential. Predictive biomarkers are crucial for optimizing the clinical use of ICIs in cancer therapy. Conclusions: While significant progress has been made, further research and collaboration among clinicians, researchers, and regulatory institutes are essential to overcome the challenges of clinical implementation. However, little is known about the relationship between local and systemic immune responses and the correlation with response to oncological therapies and patient survival.

First described some 80 years ago, pelvic exenteration remain controversial interventions with variable results and ever-changing indications. The previous studies are not homogenous and have different inclusion criteria (different populations and different disease characteristics) and methodologies (including evaluation of results), making it extremely difficult to properly assess the role of pelvic exenteration in cancer treatment. This study aims to describe the indications of pelvic exenterations, the main prognostic factors of oncologic results, and the possible complications of the intervention. Methods: For this purpose, we conducted a retrospective study of 132 patients who underwent various forms of pelvic exenterations in the Institute of Oncology “Prof. Dr. Al. Trestioreanu” in Bucharest, Romania, between 2013 and 2022, collecting sociodemographic data, characteristics of patients, information on the disease treated, data about the surgical procedure, complications, additional cancer treatments, and oncologic results. Results: The study cohort consists of gynecological, colorectal, and urinary bladder malignancies (one hundred twenty-seven patients) and five patients with complex fistulas between pelvic organs. An R0 resection was possible in 76.38% of cases, while on the rest, positive margins on resection specimens were observed. The early morbidity was 40.63% and the mortality was 2.72%. Long-term outcomes included an overall survival of 43.7 months and a median recurrence-free survival of 24.3 months. The most important determinants of OS are completeness of resection, the colorectal origin of tumor, and the presence/absence of lymphovascular invasion. Conclusions: Although still associated with high morbidity rates, pelvic exenterations can deliver important improvements in oncological outcomes in the long-term and should be considered on a case-by-case basis. A good selection of patients and an experienced surgical team can facilitate optimal risks/benefits.

Cutaneous malignant melanoma is one of the most aggressive forms of skin cancer and thus, a high mortality has been reported over decades. The prognosis for melanoma varies widely based on several factors, including the stage at which it is diagnosed, the location and thickness of the tumor, the patient's age and overall health, and specific genetic factors associated with melanoma. Therapeutic options include checkpoint inhibitors, regardless of V-Raf Murine Sarcoma Viral Oncogene Homolog B status (BRAF), and targeted therapy (anti-BRAF) in the adjuvant or metastatic setting. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but predicting which patients will benefit from these therapies remains challenging. Biomarkers like leukocytes, neutrophils, eosinophils, basophils, platelets, and other peripheral blood biomarkers have been investigated for their potential to predict responses to ICIs. Tumor mutational burden (TMB), circulating tumor DNA (ctDNA), and soluble PD-L1 (sPD-L1) have emerged as potential biomarkers for predicting responses to ICIs. Elevated baseline levels of ctDNA and elevated sPD-L1 levels have been associated with worse prognosis in melanoma patients. High TMB is often associated with better responses to ICIs in melanoma. Here we present a case from our department, of a 57-year-old patient, diagnosed in 2019 with stage IV - pT4cNx cM1 (lymph nodes metastases) and suspicion of lung metastases, BRAF wild-type right hallux malignant melanoma. Due to impressive results, first-line treatment with ICIs nivolumab and ipilimumab was the preferred treatment of choice, which showed a favorable response, with regression of oncological disease after the first cycle, and achieving complete response afterward. Unfortunately, the treatment was discontinued due to severe hepatic and pancreatic toxicity, but the favorable response to immunotherapy has been maintained for four years and is ongoing. Identifying predictive biomarkers is important to achieve the best response for the patient, with minimal adverse events, especially if long-term clinical benefit can be reached.

BACKGROUND/AIM:The application of next-generation sequencing (NGS) technology in the genetic investigation of hereditary cancer is important for clinical surveillance, therapeutic approach, and reducing the risk of developing new malignancies. The aim of the study was to explore genetic predisposition in individuals referred for hereditary cancer. MATERIALS AND METHODS:A total of 8,261 individuals were referred for multigene genetic testing, during the period 2020-2023, in the laboratory, and underwent multigene genetic testing using NGS. Among the examined individuals, 56.17% were diagnosed with breast cancer, 6.77% with ovarian cancer, 2.88% with colorectal cancer, 1.91% with prostate cancer, 6.43% were healthy with a significant family history of cancer, while 3.06% had a different type of cancer and 0.21% had not provided any information. Additionally, in 85 women with breast cancer we performed whole exome sequencing analysis. RESULTS:20% of the examined individuals carried a pathogenic variant. Specifically, 54.8% of the patients had a pathogenic variant in a clinically significant gene (BRCA1, BRCA2, PALB2, RAD51C, PMS2, CDKN2A, MLH1, MSH2, TP53, MSH6, APC, RAD51D, PTEN, RET, CDH1, MEN1, and VHL). Among the different types of pathogenic variants detected, a significant percentage (6.52%) represented copy number variation (CNV). With WES analysis, the following findings were detected: CTC1: c.880C>T, p.(Gln294*); MLH3: c.405del, p.(Asp136Metfs*2), PPM1D: c.1426_1430del, p.(Glu476Leufs*3), and SDHB: c.395A>G, p.(His132Arg). CONCLUSION:Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants' carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals.

Among urinary tract tumors, renal cancer is the most common, and regarding histopathological subtype, the clear cell type ranks first. We present the case of a patient who developed two types of solid tumors over an 11-year period. This case also highlights the role of preexisting renal lesions in the development of this cancer, the impact of early intervention on the subsequent course of the disease, as well as the importance of a multidisciplinary team in the treatment of patients with metastatic kidney cancer. Furthermore, despite the complications arising from metastatic renal cancer, the patient maintained a preserved quality of life almost two years after diagnosis.

The correlation between tumor-infiltrating lymphocytes (TILs) and immunotherapy responses is an evolving field with significant clinical implications. Immunotherapy has revolutionized antineoplastic therapies, offering promising results for patients diagnosed with solid tumors. Integrating biomarkers, refining imaging techniques, and developing non-invasive methods may enhance personalized medicine, optimizing treatment strategies while minimizing adverse effects. In our study, we conducted a retrospective analysis to assess the practicality of utilizing the predictive value of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) correlating the response to immunotherapy in patients with solid tumors, comprehensively navigating through currently available data. Continued research efforts and collaboration between scientists and clinicians are essential to unlock the full potential of these biomarkers and advance the field of immunotherapy in solid tumors.

Background: Invasive lobular carcinoma (ILC) of the breast represents approximatively 7% of all breast carcinomas and differs from invasive ductal carcinoma in terms of histological, radiological and pattern of metastases point of view. The most common spreading sites are lymph nodes, lungs and liver. At the opposite pole, ILC has been found to metastasize to the gastrointestinal tract, peritoneum and retroperitoneum, well as in gynecological organs. Adrenal gland metastasis from breast carcinoma is extremely rare being an uncommon metastatic site originating from ILC.

Cutaneous malignant melanoma is the 15th most common cancer among women, and the incidence and mortality associated with malignant melanoma continue to increase. There are several histopathological subtypes: superficial spreading, nodular, lentigo maligna, acral lentiginous, desmoplastic, and amelanotic. In this case report, we present the histopathological, local and therapeutic evolution of this aggressive pathology. A young female patient was initially diagnosed with nodular cutaneous melanoma at the lower one-third of the calf in an advanced stage, necessitating limb amputation. However, the treatment began with systemic therapy using checkpoint inhibitors as the initial therapeutic stage. Subsequently, due to resistance to this therapy and the development of an immune-related adverse reaction, targeted therapy with BRAF/MEK inhibitors was initiated, the patient presenting the positive BRAF mutation. Thus, a favorable response was achieved through the durable effects of immunotherapy and treatment with BRAF/MEK inhibitors, leading to the conversion of the lesion to a state amenable to limited resection.

Lung cancer and pulmonary tuberculosis are two significant public health problems that continue to take millions of lives each year. They may have similar symptoms and, in some cases, are diagnosed simultaneously or may have a causal relationship. In tuberculosis disease, the chronic inflammation, different produced molecules, genomic changes, and fibrosis are believed to be important factors that may promote carcinogenesis. As a reverse reaction, the development of carcinogenesis and the treatment may induce the reactivation of latent tuberculosis infection. Moreover, the recently used checkpoint inhibitors are a debatable subject since they help treat lung cancer but may lead to the reactivation of pulmonary tuberculosis and checkpoint-induced pneumonitis. Pulmonary rehabilitation is an effective intervention in post-tuberculosis patients and lung cancer patients and should be recommended to improve outcomes in these pathologies.

Melanoma is a common and aggressive tumor originating from melanocytes. The increasing incidence of cutaneous melanoma in recent last decades highlights the need for predictive biomarkers studies. Melanoma development is a complex process, involving the interplay of genetic, epigenetic, and environmental factors. Genetic aberrations include BRAF, NRAS, NF1, MAP2K1/MAP2K2, KIT, GNAQ, GNA11, CDKN2A, TERT mutations, and translocations of kinases. Epigenetic alterations involve microRNAs, non-coding RNAs, histones modifications, and abnormal DNA methylations. Genetic aberrations and epigenetic marks are important as biomarkers for the diagnosis, prognosis, and prediction of disease recurrence, and for therapeutic targets. This review summarizes our current knowledge of the genomic and epigenetic changes in melanoma and discusses the latest scientific information.

Background: Due to its many benefits, indocyanine green (ICG) has gained progressive popularity in operating rooms (ORs) globally. This literature review examines its qualitative and quantitative usage in surgical treatment. Method: Relevant terms were searched in five international databases (1. Pubmed, 2. Sciencedirect, 3. Scopus, 4. Oxfordjournals, 5. Reaxys) for a comprehensive literature review. The main benefits of using ICG in colorectal surgery are: intraoperative fluorescence angiography; fluorescence-guided lymph node involvement detection and the sentinel technique; the fluorescent emphasis of a minute liver tumour, counting just 200 tumour cells; facilitation of fistula diagnosis; and tumour tattooing. This methodology can also be used with quantitative characteristics such as maximum intensity, relative maximum intensity, and in-flow parameters such as time-to-peak, slope, and t1/2max. This article concludes that fluorescence surgery with ICG and near-infrared (NIR) light is a relatively new technology that improves anatomical and functional information, allowing more comprehensive and safer tumour removal and the preservation of important structures.

Introduction/Background Endometrial cancer (EC) is commonly associated with cardiovascular risk factors such as obesity and metabolic diseases. Especially in type 1 cancer, strong correlation with these characteristics was demonstrated. For successful holistic conduction of therapy, the patient's wish for change and compliance must be understood better. The aim of this study was to define the status quo of patient needs and preferences. Methodology An 80 item survey in paper-form and via internet was distributed to patients with diagnosed EC in seven countries. General patient characteristics (comorbidities, tumor stage, therapy), monitoring of lifestyle before and after diagnosis and adherence to treatment modalities were recorded. Results Between 12/2021 and 04/2023, 656 patients with EC (median age: 65.0[20.0; 92.0] years) completed the survey. Major recruitment took place in Germany (56%) and Switzerland (41%). The most common comorbidities were hypertension (42%), diabetes (13%) and hypothyroidism (20%). 46% of patients reported not exercising before diagnosis of EC. Only 14% increased their activity after diagnosis, 39% did even less (49% of those due to weakness). The need for medical exercise programs was low – only 30% were interested - although 55% felt that more activity would benefit their disease. 62% reported that they had not changed their diet after diagnosis. 31% would be interested in a professional nutrition counseling program, 81% did not receive one during treatment. Regarding screening programs, 52% participated in the colonoscopy program, 61% in the cervical cancer program, 34% in the skin cancer program and 71% in mammography screening. Conclusion A majority of patients believe in a potential positive impact of lifestyle changes, such as exercising and diets. Nevertheless, physical activity appeared to be relatively low and most patients did not change their diet after diagnosis. There is a need for better support of patients in these aspects, to achieve the known benefits of holistic treatment. Disclosures Financial support by GlaxoSmithKline Research & Development Limited.

Background: Alteration of the expression of human epidermal growth factor receptor-2 gene as an oncogenic pathway in breast cancer was first explored in the 1980'. Since then, tremendous progress has been made in treating HER2-positive breast cancer. Methods: We performed a narrative type review of the existing literature using as a starting point the PubMed database, investigated by keywords, later the search being refined and the articles that we considered relevant were selected. The approach to the topic under discussion being variable in the various studies identified convinced us of the inappropriateness of a meta-analysis. As a secondary method of analysis, we evaluated the bibliography of each of the selected studies and from this we identified other publications of interest. Results: At present, there are three major classes of FDA-approved anti-HER2 agents: monoclonal antibodies (Trastuzumab, Pertuzumab and Margetuximab), TKIs (Lapatinib, Neratinib and Tucatinib) and antibody-drug conjugates (T-DM1 and T-DXd). The treatment of HER2+ breast cancer suffered some changes in the last few years. If in 2018, after progression under first-line treatment with taxane-trastuzumab/pertuzumab and second line with T-DM1 was a big challenge, being up to the oncologist to choose from lapatinib-capecitabine, trastuzumab-lapatinib or different chemotherapeutic agents, depending on toxicities and therapies available in the country, nowadays we have a new third- and fourth-line FDA approved standard, which consists of tucatinib-trastuzumab-capecitabine and trastuzumab-deruxtecan. Conclusion: Times are very exciting for HER2-positive disease. What differentiates novel therapies and if we do it better is both the question that we tried to give an answer to in this review of literature, but it remains at the same time a topic of discussion and a directive for analysis in the future, because we are only getting closer to an optimal version of treatment for HER2+ breast cancer, hoping that the introduction of new drugs and the establishment of new indications for old drugs will allow us to standardize the treatment of these patients.

We present the case of a patient with breast neoplasm which presented a particular evolution with pronounced mo­le­cu­lar intratumoral heterogeneity proven at mul­ti­ple biopsies. If in the first instance, at the primary tu­mor it was discovered a negative molecular HER2 lu­mi­nal B pat­tern, in the end stage, after treatment with neo­ad­ju­vant chemotherapy, the residual tumor from the mas­tec­to­my tissue presented a luminal B profile with HER2 am­pli­fi­cation. Under targeted anti-HER2 treatment, there was cutaneous and pleural progression, lesions that were sub­jec­ted to biopsy and which revealed the presence of se­con­da­ry masses with triple negative molecular pattern.

We performed a meta-analysis of chemo-brain diagnostic, pooling sensitivities, and specificities in order to assess the accuracy of a machine-learning (ML) algorithm in breast cancer survivors previously treated with chemotherapy. We searched PubMed, Web of Science, and Scopus for eligible articles before 30 September 2022. We identified three eligible studies from which we extracted seven ML algorithms. For our data, the χ2 tests demonstrated the homogeneity of the sensitivity’s models (χ2 = 7.6987, df = 6, p-value = 0.261) and the specificities of the ML models (χ2 = 3.0151, df = 6, p-value = 0.807). The pooled area under the curve (AUC) for the overall ML models in this study was 0.914 (95%CI: 0.891–0.939) and partial AUC (restricted to observed false positive rates and normalized) was 0.844 (95%CI: 0.80–0.889). Additionally, the pooled sensitivity and pooled specificity values were 0.81 (95% CI: 0.75–0.86) and 0.82 (95% CI: 0.76–0.86), respectively. From all included ML models, support vector machine demonstrated the best test performance. ML models represent a promising, reliable modality for chemo-brain prediction in breast cancer survivors previously treated with chemotherapy, demonstrating high accuracy.

BACKGROUND:The coronavirus disease 2019 (COVID-19) pandemic outbreak forced cancer care providers to face different challenges in terms of prevention and treatment management due to specific precautions implemented for oncological patients. We aimed to describe the level of knowledge, attitude and practices (KAP) among cancer patients, with the purpose to provide an image of the impact of COVID-19 and evaluate the effectiveness of pandemic response measures.PATIENTS AND METHODS:We developed a cross-sectional multicentric study that targeted adults with active cancer during the COVID-19 outbreak, aiming to describe KAP related to COVID-19 among Romanian oncological patients. A questionnaire investigating 64 items on KAP related to the novel coronavirus was designed and applied in seven Romanian hospitals. The group of participants consisted of 1585 oncological patients who completed the questionnaire during the outbreak (April-May 2020).RESULTS:Only 172 patients (10.8%) had very good knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection symptoms, treatment options and incubation period. Only 44.3% of patients identified diarrhoea as a sign of COVID-19. About one-third of patients (32.6%) declared that they are 'very worried' about getting infected with the novel coronavirus. More than two-thirds of participants (68%) considered that having cancer represents an additional risk for infection with SARS-CoV-2, but 27.8% would rather not vaccinate against SARS-CoV-2 should a vaccine be available. A small percentage (8.8%) believed that the risk of infection justifies delaying/stopping oncological treatment until after the pandemic. Around half of the participants (55.5%) declared being compliant with all the protective measures against coronavirus infection listed in the questionnaire.CONCLUSION:Romanian oncological patients have a less than expected knowledge about SARS-CoV-2, appropriate prevention behaviours, with limited trust in their efficacy, optimistic attitudes towards COVID-19 and low level of trust in information sources. Good COVID-19 knowledge was associated with appropriate practices towards COVID-19 and optimistic attitudes.