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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Copyright of Oncolog-Hematolog is the property of MEDICHUB MEDIA, S.R.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Alteration of the expression of human epidermal growth factor receptor2 gene as an oncogenic pathway in breast cancer was first explored in the 1980s. 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, using keywords, with the search being refined later and the relevant articles being selected. As the approaches to the topic under discussion were different in various studies, we were convinced of the inappropriateness of a metaanalysis. 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 TDXd). The treatment of HER2+ breast cancer has suffered some changes in the last few years. If in 2018, progression under first-line treatment with taxanetrastuzumab/pertuzumab and second line with T-DM1 was a big challenge, and it was 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: The question of how to improve novel therapies to treat HER2-positive disease remains a topic of discussion 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. [ABSTRACT FROM AUTHOR]

Melanoma is a public health issue due to its increasing incidence and young age of diagnosis. There are three types of malignant melanoma: cutaneous, uveal and mucosal, all with different incidence, prognosis and management. Some malignant melanoma treatments – including chemotherapy, targeted therapies, immunotherapy and radiation – can change the immune response. People with weakened immune systems or with lung problems due to radiotherapy pneumonitis or immune-mediated pneumonitis or with lung metastases have a much higher risk of complications if they are infected with SARS-CoV-2. On the 20th of April 2020, there were reported 2,444,209 coronavirus cases and 167,986 deaths. There are various recommendations amidst COVID-19 pandemic on diagnosis and treatment of patients with different kinds of solid tumors. The ethical principle that should guide our medical decisions should be primum non nocere, respecting patient wish and trying to do what is best for him/her, with fair allocation of resources. In this review, we wanted to evaluate and reinforce the recommendations on melanoma patients' management by searching for different medical societies' recommendation. We found guidelines on how to manage melanoma patients in different stages of the disease and how to treat best patients, minimizing exposure to infection. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of cancer in women worldwide and the second cause of cancer in both sexes. In Romania, it is the leading cause of cancer, according to Cancer Country Profile 2020. Some breast cancer treatments – including chemotherapy, targeted therapies and radiation – can weaken the immune system. People with weakened immune systems or lung problems due to radiotherapy pneumonitis or with lung metastases have a much higher risk of complications if they are infected with SARS-CoV-2. On the 20th of April 2020, there were reported 2,444,209 coronavirus cases and 167,986 deaths. There are various recommendations amidst COVID-19 pandemic on the diagnostic and treatment of patients with different kinds of solid tumors. Almost all professional societies try to identify the optimal protocols for cancer facilities, to minimize the risk of SARS-CoV-2 infection in both inpatient and outpatient settings. Due to the coronavirus pandemic, routine checkups, elective, unnecessary surgeries and other procedures have been cut back or delayed to help minimize exposure to the virus which has already infected more than 2.4 million people. The recommendations were divided according to the phase of pandemic manifestations on different countries and according to priority. In this review, we want to reinforce and bring together all recommendations made by different societies involved in the treatment management of breast cancer patients, because this pandemic led to new ways of dealing cancer patients. [ABSTRACT FROM AUTHOR]

Copyright of Oncolog-Hematolog is the property of MEDICHUB MEDIA, S.R.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Antineoplastic targeted therapies, such as EGFR inhibitors, tyrosine kinase inhibitors and BRAF inhibitors, frequently lead to systemic and cutaneous side effects, significantly affecting patient's quality of life. Patients with new targeted therapies have an increased risk of developing skin reactions. The new molecular target therapies developed in the last decades can induce severe skin reactions, which may require dose reduction or discontinuation of treatment and consequently, a decrease in patient's quality of life. The present paper describes toxic cutaneous reactions associated with the most frequently used molecular therapies (epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, BRAF-inhibitors), frequency of occurrence and methods of diagnosis and treatment, in order to offer a clinically efficient management for maintaining a good quality of life, with compliance to treatment and good therapeutic efficacy. Knowledge of cutaneous adverse reactions in new therapies is mandatory in order to have a proper management of oncologic patients. Recognizing target therapy toxicities by both oncologists and dermatologists, understanding therapeutic mechanisms and choosing optimum treatments for oncologic patients are critical. A correct evaluation of skin toxicity can allow for an adequate decision regarding treatment dose or discontinuation, impacting therapy response and patient survival. [ABSTRACT FROM AUTHOR]

Background. Advances in early diagnosis and the development of treatments in breast cancer have led to improvements of disease-free and overall survival. Chemotherapy and targeted therapies induced cardiotoxicity is concerning, and the cardiovascular side effects can impact the quality of life and survival. Cardiac risk factors should be assessed when deciding on treatment regimens for breast cancer. Methods. The study aims to determine risk factors favoring cardiac-induced toxicity of trastuzumab in patients treated at the “Prof. Dr. Al. Trestioreanu” Institute of Oncology Bucharest within four years, from 2010 to 2013. The study included 368 patients diagnosed with breast cancer, HER2/neu-positive with neoadjuvant/adjuvant chemotherapy and adjuvant trastuzumab. The primary study objective is to determine the incidence of cardiotoxicity and the impact of risk factors among patients with breast cancer, HER2/neu-positive, treated with trastuzumab and anthracycline compared to literature. The second objective is establishing the proportion of patients who experienced reversible cardiotoxicity and clinical manifestations related cardiotoxicity, following treatment with trastuzumab and anthracyclines. Results. The analysis showed that adjuvant treatment was indicated in 257 patients and that 111 patients had metastatic disease, of which 44 patients were treated with trastuzumab in adjuvant setting and 67 were naive to treatment with trastuzumab. Patients receveing trastuzumab had the following risk factors for cardiotoxicity: increased body mass index, smoking, sedentary, high cholesterol, high blood pressure, diabetes. Reversible cardiotoxicity was noticed in 16% of the cases (from the total of 368 patients) and required the temporary interruption of the administration of trastuzumab, and one patient with trastuzumab developed irreversible cardiotoxicity. 16 patients had symptomatic heart failure. The study results showed that administering trastuzumab to women with these cardiovascular risk factors led to increased cardiotoxicity and the reduction of LVEF, requiring temporary interruption of trastuzumab. Conclusions. Early recognition of cardiac toxicity can lead to improvement in cardiac survival and patient outcomes. The focus of this review was to summarize the cancer therapy agents most often associated with cardiovascular side effects, highlighting the risk factors that can be improved and strategies for surveillance and prevention. The incidence of cardiotoxicity and the impact of risk factors among patients with breast cancer, HER2/neu-positive, treated with trastuzumab and anthracycline, are similar to those presented in data from literature. Early identification of individuals at risk and monitoring patients during chemotherapy are very important, and they can facilitate early intervention with cardioprotective medications or adjustments to the chemotherapy regimen. [ABSTRACT FROM AUTHOR]

The incidence of colorectal cancer in the European Union is in continuous growth and approximately 15% of the cases present with a hereditary component, the most frequently encountered associations being with the Lynch syndrome and familial adenomatous polyposis. Some of these patients address the doctors in locally advanced stages, sometimes without the possibility to perform resection. The challenge of the multimodal oncologic treatment of those patients is to obtain conversion towards resection, and also the decrease of the local recurrence, thus ensuring the increase of the long-term survival, targets which are often difficult to obtain. We present the case of a 54-year-old patient with locally advanced rectal cancer, who benefitted from multimodal treatment: neo-adjuvant chemotherapy and radiotherapy, and also from surgical intervention. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy involves the use of therapeutic modalities that determine a manipulation of the immune system by using immune agents such as cytokines, vaccines, cell therapies and humoral, transfection agents. Immunotherapy of cancer has to stimulate the host's anti-tumor response by increasing the effector cell number and the production of soluble mediators and decrease the host's suppressor mechanisms by inducing tumor killing environment and by modulating immune checkpoints. Immunotherapy seems to work better in more immunogenic tumors. Making a review of literature, the article presents the new immunologic treatments in cancers less presented in the latest conferences, cancers in which, immunotherapy is still under investigation. Bladder cancer was the first indication for which immunotherapy was used in 1970. A promising clinical research in bladder cancer is the use of immune checkpoint inhibitors. Although breast cancer is considered immunologically silent, several preclinical and clinical studies suggested that immunotherapy has the potential to improve the clinical outcomes for patients with breast cancer. Cervical cancer, brain cancer, head and neck cancer and colorectal and esophageal cancers are cancer types for which new immune-based cancer treatments are currently under development. Recent agents used in clinical trials will be described in before mentioned cancers. [ABSTRACT FROM AUTHOR]

Copyright of Oncolog-Hematolog is the property of MEDICHUB MEDIA, S.R.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nephroblastoma or Wilms' tumor is the most common renal tumor in children, only 3% of all cases are encountered in young adults. The main differential diagnoses is clear cell renal carcinoma, with similar clinical presentation, but different immunohistochemically staining. Approximately 10% of children diagnosed with Wilms'tumour have certain congenital defects (aniridia, hemi-hypertrophy or cryptorchidism). Syndromes linked to nephroblastoma include WAGR syndrome, Beckwith- Wiedemann syndrome, Deny's-Drash syndrome or trisomy 18. Adult Wilms'tumour has a poorer prognosis than pediatric Wilms tumour. Agressive treatment with multimodal approach involving surgery, chemotherapy and radiotherapy, according with pediatric NWTS guidelines showed an overall 5-year survival rate of 7085% in some clinical trials. Because of its low incidence rate, prognostic variables have not been studied on a large cohort of patients. Here, we raport a case of a 20-year-old patient with stage IV Wilms tumour, with lung and bone metastasis, with unfavourable histopathology (anaplasia) treated on a pediatric protocol, with multimodal approach. [ABSTRACT FROM AUTHOR]

This case study refers to a patient with neuroendocrine small cell lung cancer with lung metastases. The immunohistochemistry confirms the results of histopathology exam. The patient was treated by chemotherapy with cisplatin end etoposid. The outcome was stabled disease. Case argues the use of positron emission tomography and alphafetoprotein in pursuing therapeutic result. [ABSTRACT FROM AUTHOR]

Malignant melanoma is a disease with unpredictable response to systemic treatments. Now, there are targeted treatments available - Ipilimumab and Vemurafenib which changed prognosis of this disease. We proposed to present one experience of Medical Oncology Department in Institute of Oncology Bucharest - in treatment of metastatic ocular malignant melanoma with Ipilimumab, treatment sustained by BMS. We will show one case with complete response - case with oii go met astatic disease treated with Ipilimumab: one young patient, 36 years old, with operated malignant ocular melanoma which developed lymph node metastases at 8 months añer surgical intervention. Patient ended 4 cycles of Ipilimumab with no adverse reaction. Therapeutic response at the end of treatment was complete response which is maintained at 6 and 12 months añer treatment. In conclusion, ocular melanoma is a rare disease with low response to classic treatments, rare BRAF mutation. Can we eradicate oii gom eta static ocular melanoma disease with Ipilimumab? How long can response last? [ABSTRACT FROM AUTHOR]

Copyright of Oncolog-Hematolog is the property of MEDICHUB MEDIA, S.R.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Breast cancer clinically represents a heterogeneous disease. Over decades, the integration of prognostic and predictive markers in the treatment decisions has led to a more individualized and optimized therapy. The prognosis describes the risk of disease recurrence and disease-related death after diagnosis without the influence of therapy, and the prediction illustrates the probability of efficacy or response of a specific therapeutic measure. The present study evaluated the clinical significance of Ki-67 index, ER, PGR, cerb-2 and Her2 receptors as prognostic markers and predictors of recurrence in different molecular subtypes of breast cancer. We analyzed the relationship of these receptors with different clinicopathological factors. We have processed samples from 130 patients hospitalized in the Third Surgery Department of the “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest. The biological samples were taken by breast biopsy punctures or by excision of the tumors, and we analyzed them histopathologically and immunohistochemically. The improved understanding of breast cancer biology and genetics together with the utilization of the classical biomarkers and the identification of new markers or profiles are increasingly defining the clinical decisions that are to be made in order to minimize overtreatment, undertreatment and incorrect treatment. [ABSTRACT FROM AUTHOR]

Ocular melanoma is a distinct entity with an increasing incidence in recent years. The incidence of ocular melanomas in the USA, according to Surveillance, Epidemiology and End Results (SEER), is 0.69/100,000 people per year in men and 0.54/100,000 people per year in women. Ocular melanoma has a particular prognosis and treatment. It represents 5% of all melanomas. Among ocular malignancies, melanomas are the most common. 13% of the deaths due to melanoma are caused by ocular melanoma because of the increased metastatic rate and poor response to treatment. Metastases occur in 31% of patients at 5 years, 45% at 15 years and 50% at 25 years, according to Collaborative Ocular Melanoma Study Group (COMS). Metastases in the liver are the most common - 89% of patients with metastasis. The death rate from metastasis is 80% at 1 year and 92% at 2 years. In recent years, the mutations that occur in ocular melanoma and treatment options have been extensively researched. The results obtained with various systemic therapies are disappointing. In this paper we intend to present prognostic factors and treatment modalities. [ABSTRACT FROM AUTHOR]

Metastatic renal cancer is an important field regarding targeted therapy in oncology. If until the early 1990s we were only talking about immunologic treatment with high doses of interleukin 2 and alpha-interferon, starting with 2005 and 2006, antiangiogenic therapy appeared in the therapeutic arsenal and two new molecules, sorafenib and sunitinib, were approved for use. R.J. Motzer's study of sunitinib versus interferon- alpha treatment of naïve patients with metastatic disease and the clear cell carcinoma histological subtype published in New England Journal of Medicine in 2007 resulted in a double progression-free survival (PFS) - over 11 months versus 5 months for sunitinib, with p<0.001, and a convenient toxicity profile. In 2007, bevacizumab was registered in the first line of treatment for the same group of patients, a monoclonal antibody with antiangiogenic effect, following the study of AVOREN and CALGB 90206 (median PFS 10.2 months vs. 5.4 months). In case of “poor risk” renal cancer, the phase III ARCC study established the role of the mTOR inhibitor for this category of patients with an overall survival of 10.9 months and a statistically significant PFS. In 2010, another antiangiogenic TKI inhibitor, pazopanib, was recorded due to VEG 105192 study results, with a 54% reduction in risk of progression or death compared with placebo and a significant increase in PFS in all subgroups of patients. Anticipating the EMA requirement, the COMPARZ study was initiated, a head-to-head non-inferiority study comparing this molecule with sunitinib, because the data showed similar results of the two molecules in terms of effectiveness and safety profile. The results of the registration studies for the two molecules, sunitinib and pazopanib, have been confirmed by real-world data, along with data from the extended access programs. The results of the International Mrcc database Consortium confirmed the clinical results for sunitinb and pazopanib. In conclusion, the treatment line for metastatic renal cancer has remained unchanged from 2010 until now. [ABSTRACT FROM AUTHOR]

Bladder cancer is the seventh cause of cancer death in men and the tenth in women. In metastatic disease, the prognosis remains poor, with a median survival of 15 months. Chemotherapy has remained standard systemic therapy over the past 15 years for patients with recurrent or metastatic disease. The therapeutic regimens recommended by guides in metastatic disease, as the first treatment line, are the combination of gemcitabine and platinum salts or the MVAC combination. Currently, there is no second-line standard systemic therapy for patients with tumor relapse after first-line chemotherapy. Therefore, the treatment of advanced and metastatic urothelial tumors remains a challenge for oncologists. Following radical cystectomy, more than half of patients with invasive urothelial carcinoma will develop recurrent disease. The excellent results obtained in the treatment of other solid tumors using targeted therapies such as tyrosine kinase inhibitors or CTLA-4 anti-CTL-4 or PD1 inhibitor immunotherapy have led to the idea that these therapies could be used with promising results in the treatment of metastatic bladder cancer. The acquisition of mutations in the PI3K/AKT/mTOR intracellular signal transduction pathway has been demonstrated in over 40% of bladder cancers, suggesting that blocking the mTOR pathway would be a promising target therapy in this pathology. Starting from this idea, there are currently several phase I and II studies of mTOR inhibitors like temsirolimus or sirolimus, the preliminary results being encouraging. In terms of immunotherapy in metastatic bladder cancer, there are currently several phase I or phase II studies testing anti-CTLA-4 therapy (ipilimumab) or PD1 inhibitors (nivolumab). Besides these molecules, there are studies that test new molecules such as MPDL3280A, MEDI4736 and MK3475 (lambrolizumab). All preliminary data show the efficacy of these new therapies in metastatic urothelial carcinoma. Our paper aims to review these new therapies by presenting the undergoing studies for recurrent and metastatic urothelial carcinoma with the preliminary results and safety profile of these new agents. In the future, we will have a new standard in the systemic treatment of advanced and metastatic urothelial carcinomas. [ABSTRACT FROM AUTHOR]

Ovarian cancers are among the most deadly cancers, because only 20% are detected in early stages and only 30% of patients survive at 5 years. These data plead why translational medicine has developed regarding cancer, because a tumor is being considered heterogeneous and a single treatment cannot treat all forms of ovarian cancer. Based on the molecular classification of ovarian cancers, new opportunities for translational medicine have been born. Taking into account the main histological subtypes of ovarian cancer and associated mutations or chromosomal aberrations, the main targets, the appropriate therapy and the clinical implications are analyzed in this presentation. [ABSTRACT FROM AUTHOR]

Targeted molecular therapy is the newest and most dynamic chapter of current oncology research, boosted by the recent complete decoding of the human genome. The most commonly used classes of molecular drugs currently include: small molecule tyrosine kinase inhibitors (TKI) and multikinase inhibitors, monoclonal antibody blocking transduction signals, angiogenesis inhibitors, proteasome inhibitors, histone deacetylase inhibitors and demethylation agents, epigenetic therapy, differentiation agents, gene therapy strategies and vaccines. Although targeted therapies are considered to be less toxic and better tolerated by patients compared to classical chemotherapeutic agents, rare but severe complications have been described, and longer follow-up is required to determine the exact profile and prognosis of associated cardiac adverse reactions. Both conventional chemotherapy and targeted molecular therapies are associated with well-defined short-term and long-term risks of cardiovascular events. Because these agents are commonly used for curative purposes, benefits maximization and concomitant reduction of cardiac risk have become a priority in oncology management, as well as monitoring to identify late toxicity. [ABSTRACT FROM AUTHOR]