The Efficacy of Immunotherapy in Long-Term Survival in Non-Small Cell Lung Cancer (NSCLC) Associated with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).

INTRODUCTION: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in cancer patients, occurring most frequently in patients with small cell lung cancer. However, this syndrome occurs extremely rarely in patients with non-small cell lung cancer. The results of the clinical trials have revealed that immuno-oncological therapies are effective for long periods of time, providing hope for long survival and with a good quality of life. CASE PRESENTATION: We present the case of a female patient who was 62 years old at the time of diagnosis in 2016 who underwent surgery for a right pulmonary tumor (pulmonary adenocarcinoma) and subsequently underwent adjuvant chemotherapy. The patient had a left inoperable mediastinohilar relapse in 2018, which was treated using polychemotherapy The patient also had an occurrence of progressive metastasis and a syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 2019 for which immunotherapy was initiated. The patient has continued with immunotherapy until the time this study began to be written (April 2023), the results being the remission of hyponatremia, the clinical benefits and long-term survival. DISCUSSION: The main therapeutic option for SIADH in cancer patients is the treatment of the underlying disease, and its correction depends almost exclusively on a good response to oncological therapy. The initiation of immunotherapy at the time of severe hyponatremia occurrence led to its remission as well as the remission of the other two episodes of hyponatremia, which the patient presented throughout the evolution of the disease, demonstrating an obvious causal relationship between SIADH and the favorable response to immunotherapy. CONCLUSIONS: Each patient must be approached individually, taking into account the various particular aspects. Immunotherapy proves to be the innovative treatment that contributes to increasing the survival of patients with metastatic non-small cell lung cancer and to increasing their quality of life.

An Overview of Cytomegalovirus Infection in Pregnancy.

The objective of this review was to bring to attention cytomegalovirus (CMV) infection during pregnancy, taking into consideration all relevant aspects, such as maternal diagnosis, fetal infection and prevention, prenatal diagnosis, and postnatal prognosis. A literature review was performed regarding adult and congenital infection. General information regarding this viral infection and potential related medical conditions was provided, considering the issues of maternal infection during pregnancy, transmission to the fetus, and associated congenital infection management. Prenatal diagnosis includes maternal serum testing and the confirmation of the infection in amniotic fluid or fetal blood. Additionally, prenatal diagnosis requires imaging techniques, ultrasound, and complementary magnetic resonance to assess cortical and extracortical anomalies. Imaging findings can predict both fetal involvement and the postnatal prognosis of the newborn, but they are difficult to assess, even for highly trained physicians. In regard to fetal sequelae, the early diagnosis of a potential fetal infection is crucial, and methods to decrease fetal involvement should be considered. Postnatal evaluation is also important, because many newborns may be asymptomatic and clinical anomalies can be diagnosed when sequelae are permanent.

A Real-World Study to Compare the Safety and Efficacy of Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir, with or without Ribavirin, in 587 Patients with Chronic Hepatitis C at the Fundeni Clinical Institute, Bucharest, Romania.

BACKGROUND In the European Union, a tablet with fixed doses of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir is an authorized treatment for patients with chronic hepatitis C virus (HCV) infection. Ribavirin is a broad-spectrum antiviral used in several treatment regimens for patients with HCV infection. This real-world study aimed to compare the safety and efficacy of ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin, in 587 patients with chronic hepatitis C attending the Fundeni Clinical Institute, Bucharest, Romania. MATERIAL AND METHODS This is an observational prospective study including 315 patients with F4 degree of fibrosis and compensated cirrhosis, 185 patients with F3 fibrosis, and 83 patients with F2 fibrosis. Liver fibrosis was evaluated by liver biopsy or Fibromax. Efficacy was defined as undetectable HCV-RNA at 12 weeks after the end of treatment. In terms of safety, we monitored the development of adverse reactions, liver cytolysis, cholestasis, and hematologic disorders. RESULTS Of the 587 patients, 2 patients with B-cell lymphoma died during therapy. In total, 3/585 patients (0.51%) did not achieve sustained virologic response. Common adverse effects were nausea and asthenia (especially in patients with other medical treatments; P=0.03 and P=0.04, respectively) and anemia in patients who received ribavirin (P<0.01). None of the patients discontinued antiviral treatment. Patients with kidney transplant or end-stage kidney disease did not receive or discontinued ribavirin. CONCLUSIONS Ombitasvir, paritaprevir, and ritonavir combined with dasabuvir, with or without ribavirin had an efficacy rate of over 99% in HCV genotype 1b infection. We report no serious adverse reactions.

A review of NTRK fusions in cancer.

The family of the neurotrophic tropomyosin kinase receptors (NTRK or TRK) is a part of the transmembrane tyrosine kinases responsible for neuronal development. The members of this receptor family are TRKA, TRKB and TRKC and they are encoded by the genes NTRK1, NTRK2 and NTRK3. Alterations of NTRK genes can induce carcinogenesis both in neurogenic and non-neurogenic cells. The prevalence of NTRK gene fusion is under 1% in solid tumors, but is highly encountered in rare tumors. The presence of NTRK 1 gene fusion is associated, in some types of neoplasia, with a favorable evolution, but the presence of NTRK 2 may be associated with a poor prognosis. The identification of cancer patients harboring NTRK gene fusions is constantly growing, especially with the advent of NTRK inhibitors. This has promisingly provided a rationale for personalized therapeutics that improved outcomes in settings with this signature.

Glycemic Control in Patients Undergoing Treatment With Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir for Chronic Hepatitis C Infection.

BACKGROUND/AIM: Patients with hepatitis C virus (HCV)-associated cirrhosis are more prone to developing type 2 diabetes mellitus than patients with any other etiology of cirrhosis. The main objective of this study was to evaluate the impact of all oral antiviral treatment with ritonavir-boosted paritaprevir/ombitasvir and dasabuvir (OBV/PTV/r + DSV) in patients with chronic genotype 1b HCV infection. PATIENTS AND METHODS: We retrospectively evaluated 806 patients who underwent antiviral therapy between December 2015 and July 2019. The laboratory data analyzed were liver function tests, kidney function tests, HCV viremia, fasting glucose levels, and glycosylated hemoglobin. RESULTS: Patients with impaired glucose metabolism were predominantly male and of older age compared to patients with normal glucose tolerance, and also had higher levels of transaminases. Proteinuria and higher creatinine levels were found in patients with impaired glucose metabolism. Overall, we found a 98.01% rate of sustained virologic response (SVR), with a non-significant difference between patients with normal and abnormal glucose metabolism. A statistically significant difference in SVR rates in patients with low degrees of fibrosis (F0-F2) versus those with advanced degrees of fibrosis (F3-F4) was found in both groups. Antiviral treatment resulted in significant decreases in fasting glucose levels and glycosylated hemoglobin levels in all patients with impaired glucose metabolism at SVR. CONCLUSION: Patients with pre-diabetes, as well as diabetic patients, achieved a better glycemic control after SVR obtained by ritonavir-boosted paritaprevir/ombitasvir and dasabuvir.

Impact of the COVID-19 Pandemic on Treatment and Oncologic Outcomes for Cancer Patients in Romania.

BACKGROUND/AIM: This study aimed to assess the impact of the ongoing COVID-19 pandemic on cancer patients, known to be immune-compromised due to the disease itself, oncological treatments and adjuvant medicines use such as steroids. Overall survival was determined for patients with COVID-19 infection and stratification according to known comorbidities and complications was performed. PATIENTS AND METHODS: This prospective study included ninety cancer patients with COVID-19 confirmed by PCR testing performed before each cycle of chemotherapy or every two weeks during radiotherapy between May and December 2020 in two tertiary Cancer Centers. Demographic, cancer-related and SARS-CoV-2 infection data were collected and long-term oncologic outcome was assessed. RESULTS: Mean age of cancer patients diagnosed with SARS-CoV-2 was 59.7±12.1 years (range=30-83 years). Fifty-two (57.7%) were women. The most frequent cancer localization was breast (n=28, 31.1%) followed by colorectal (n=11, 12.2%) and lung cancer (n=8, 8.8%). Most patients infected with SARS-CoV-2 were diagnosed in stage IV of the disease (n=44, 48.9%) followed by stage III (n=19, 21.1%) and stage II disease (18.9%). Regarding comorbidities, the most common was hypertension (n=31) followed by cardiac dysfunction (n=23) and type II diabetes (n=13). Of 27 (30%) patients who needed hospitalization, 4 patients developed severe infection, 17 patients had mild symptoms and 6 patients were minimally symptomatic. After a median follow-up of 22.5 months, 5 patients (5.55%) died due to SARS-COV-2 infection, all stages III and IV. Median estimated overall survival was 14 months in patients who died because of COVID infection compared to 98 months in cancer-related mortality analysis (p<0.0001). Three deaths occurred during chemotherapy, 1 death in the chemoradiotherapy radiotherapy group. CONCLUSION: SARS-CoV-2 infection was associated with an excess mortality in our study population, especially in patients with advanced and metastatic disease and in those receiving immunosuppressive treatment such as chemotherapy and radiotherapy.

The Role of Programmed Cell Death Receptor 1 in Lung Cancer.

BACKGROUND/AIM: Lung cancer is the most common cancer worldwide. Cancer immunotherapy is the activation of the immune system against cancer. The latest method of immunotherapy involves immune checkpoint inhibitors. Increased levels of programmed death ligand 1 (PD-L1) expression were observed on non-small-cell lung cancer. The association between PD-L1 expression and clinicopathological characteristics in lung cancer is still unclear. PATIENTS AND METHODS: This is a cross-sectional, observational study that evaluated a sample of 41 lung cancer patients diagnosed between March 2019 and December 2020. PD-L1 tumor expression is described as a percentage. RESULTS: Patients were diagnosed with non-microcellular lung cancer and aged 37 to 87 years. Most patients were diagnosed with adenocarcinoma. According to the analysis, the average age of patients with negative PD-L1 tumors was 65.6 years, and of those with positive PD-L1 tumors was 63.6 years. The average value of the tumor proportion score for males was 26.97%, and for females 25.55%. CONCLUSION: No correlation was found between PD-L1 tumor expression and the age and sex of patients.

Quantitative Analysis of SPECT-CT Data in Metastatic Breast Cancer Patients-The Clinical Significance.

PURPOSE: To assess the potential added value of the SPECT-CT quantitative analysis in metastatic breast cancer lesions detection and differentiation from degenerative lesions. METHODS: This prospective monocentric study was conducted on 70 female patients who underwent SPECT-CT bone scans using 99mTc-HDP that identified the presence of metastatic bone lesions and degenerative lesions in each patient. Once the lesions were identified, a quantitative analysis of radiotracer uptake was conducted. The highest one to five SUVmax values for both metastatic and degenerative bone lesions were identified in each patient and the data were then statistically analyzed. RESULTS: The SUVmax value was significantly higher in metastatic bone lesions than in degenerative lesions (p < 0.001). The diagnostic accuracy of SPECT-CT quantitative data analysis revealed a sensitivity of 91.5% and a specificity of 93.3% at a cut-off value of the SUVmax of 16.6 g/mL. CONCLUSION: Quantitative analysis performed using SPECT-CT data can improve the diagnostic accuracy in differentiating between metastatic bone lesions and degenerative lesions, thus leading to appropriate treatment and better follow-up in metastatic breast cancer patients.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

Long-term Response After Stopping Immunotherapy in a Patient With Metastatic Renal Cancer.

BACKGROUND/AIM: Kidney cancers account for about 2% of human malignancies. In recent decades, the incidence of this cancer type has gradually increased, mainly due to advances in imaging. The metastatic potential of these cancers is significant: a quarter of patients will immediately present with metastases and more than one third of patients treated with nephrectomy for a localized disease will develop metastases during their course. In total, more than half of patients will suffer from the consequences of metastasis. The median survival at this stage is only thirteen months, so the therapeutic challenge is immense. CASE REPORT: The present case report describes a case of left renal clear cell carcinoma with brain, lung, right adrenal, bone and lymph node metastases in a 55-year-old male. The patient received only one line of anticancer treatment with sunitinib, which could not be continued due to haemorrhagic manifestations in brain metastases. The treatment was changed with immunotherapy which showed its effect even if it was stopped due to the patient wishes in the context of the COVID-19 epidemic. CONCLUSION: Immunotherapy opens the doors to a new era in treatment of metastatic renal cancer and shows efficiency even after it has been stopped.

Lung Cancer, Covid-19 Infections and Chemotherapy.

BACKGROUND/AIM: The Covid-19 epidemic has severely strained health care systems across the globe. The impacts are multiple especially for patients cared for cancer. The Covid-19 epidemic has several impacts on the management of lung cancer patients. The aim of this work was to summarize the available epidemiological data on patients diagnosed with lung cancer infected with Covid-19 and describe the different strategies to improve the management of these patients by summarizing the recommendations in this area. PATIENTS AND METHODS: The Teravolt cohort is an observational multicenter registry, including patients with non-small cell cancer, small cell cancer or mesothelioma but also epithelial tumors and a diagnosis of Covid-19. The Theravolt registry indicates an unexpectedly high mortality rate in patients with thoracic malignancies with COVID-19. RESULTS: Between March 26 and April 12, 2020, 200 patients treated in 8 countries were included. They had a performance status (PS) of 0-1 in 72% of cases, were smokers or ex-smokers in 81% of cases, had non-small cell cancer (76% of cases), were under treatment in 74% of cases, and the majority were first-line cases (57%). The hospitalization rate was 76% and the mortality rate 33%; only 10% of patients with criteria for intensive care hospitalization were admitted to the intensive care. CONCLUSION: Data presented in this registry suggest a high mortality in patients with thoracic cancer and Covid-19. Therofere, the importance to create a safe healthcare system during Covid-19 pandemic is underlined along with the need for essential effective clinical service delivery to patients with lung cancer.

Cutaneous and Inguinal Lymph Nodes Metastases Disseminated from an Endometrial Serous Carcinoma - Case Report and Literature Review.

Cutaneous metastases from endometrial cancer are rare and unusual. This is the case of a 72 years old female patient, diagnosed in 2018 with G3 endometrial serous carcinoma (ESC). At 18 months from the surgical intervention, the patient developed bilateral inguinal lymph nodes metastases and skin secondary lesions; histological and immunohistochemical tests were performed. Computed tomography scan did not indicate visceral secondary lesions, local or regional relapses. We present the treatment practiced, the case's evolution and we discuss about epidemiology, molecular biology, treatment options and management of advanced and local lesions. The appearance of skin metastases in theses cases is associated with poor prognosis and treatment options are limited to palliative chemotherapy and radiotherapy.

Management of Diagnosis and Treatment in a Case of Fibrolamellar Carcinoma.

Background/Aim: Fibrolamellar carcinoma is a rare primary hepatic malignancy that has recently been recognized as a distinct clinical entity, highly different from the well-known hepatocellular carcinoma. This report describes the clinical and paraclinical aspects of the fibrolamellar carcinoma, emphasizing its particularities. Case Report: A 30-year-old patient presented to the hospital with nonspecific symptoms and weight loss, with imaging findings showing abdominal and mediastinal masses. Multiple biopsies were performed, leading to a diagnosis of metastatic fibrolamellar carcinoma. Given the extent of the disease, systemic drug treatment was administered, although prognosis was poor with tumor growth, resulting in biliary duct invasion. Conclusion: Fibrolamellar carcinoma is a rare type of malignancy, with a difficult differential diagnosis in which imaging techniques are important but for which biopsy remains the gold standard. The prognosis depends on tumor extent and may include surgical methods or chemotherapy.

Biomolecular Factors Represented by Bcl-2, p53, and Tumor-Infiltrating Lymphocytes Predict Response for Adjuvant Anthracycline Chemotherapy in Patients with Early Triple-Negative Breast Cancer.

Treatment of triple-negative breast cancer is challenging. Standard adjuvant tretment is considered to be the cobination of anthracycline and taxanes although the role of anthracyclines administered preoperatively  remains controversial. Actually, some studies recommended taxane-only regimens. We reviewed literatures to examine whether tissue biomarkers available in an ordinary laboratory setting (eg, haematoxylin and eosin and immunohistochemistry) may predict response to adjuvant anthracyclines in patients with triple-negative breast cancer. Our review showed that Bcl-2, p53, and tumor-infiltrating lymphocytes (TILs) expression may become independent predictors for triple-negative breast cancer. This finding was based on data from retrospective studies, and, thus, randomized controlled study is needed to confirm the present results.

Pathologic Response After Weekly Paclitaxel versus Docetaxel in Operable Breast Cancer.

INTRODUCTION: Weekly paclitaxel (Ptx) and q3w docetaxel (Dtx) are equivalent in adjuvant breast cancer treatment. Weekly Ptx is better tolerated than q3w Dtx and became the first choice in daily practice, even preoperatively. METHODS: To compare the efficacy and safety of the two regimens, a retrospective analysis was performed in breast cancer patients (pts) referred for neoadjuvant, sequential, taxane-containing chemotherapy to the Institute of Oncology and Oncofort Clinic, Bucharest, between 2008 and 2017. RESULTS: Forty-seven cases were eligible, median age was 56 years (34-73 years), mainly stage IIIA-B (53.2%, 25 pts) and ductal invasive (70.2%, 33 pts) of which 24 pts (51%) received q3w Dtx and 23 pts (48.9%) weekly Ptx. The histological response rates were 62.5% (15 pts) and 73.7% (17 pts) (p=0.47), average dose-intensity was 87.7% and 96.7% (p=0.002) and grade III-IV toxicity rate was 12.5% and 13% (p=0.64), respectively. Pathologic response was correlated with immunophenotype, PgR expression, tumor size and backbone chemotherapy (p<0.05). DISCUSSION: Our study showed an improved efficacy of taxane's weekly administration, probably due to a better tolerance and a lower rate of dose-impairing toxicities.

Rare Pelvic Malignant Tumors in Adults: Treatment Features and Clinical Outcome in Nonmetastatic Disease (Single Institution Experience).

BACKGROUND: Nearly 200 cancers repertories are rare, and more than 20% are pelvic neoplasia. Diagnosis and treatment are challenging, even in reference centers, and survival is influenced by the aggressiveness of certain histologies and absence of a standard of care. PATIENTS AND METHODS: The authors report the results of a retrospective analysis of patients that attended the Institute of Oncology, Bucharest, between 2004 and 2015, for nonmetastatic pelvic malignant tumor treatment and follow-up. The outcomes are compared between the rare and common histology groups. RESULTS: Of the 60 cases analyzed, 17 patients (28.33%) bore a rare tumor, 33 (55%) were women, and the median age was 59 years. The majority was concerned by bladder (41.66%, 25 patients) and cervix (23.33%, 14 patients) neoplasms. For a median follow-up of 27.5 months, relapse was registered in 27 patients (45%), of whom 9 (33.33%) were from the rare group (53% of this subpopulation). The highest relapse rates were recorded in patients with rare bladder tumors (66.7%, 4 patients) compared with 42.1% (8 patients) in the common group (p = 0.294) and in prostate localization (66.7%, 2 patients) compared with 16.7% (1 patient) (p = 0.134). Estimated median relapse-free survival (RFS) was 60, 12 months in the rare group and 67 months for common tumors. CONCLUSIONS: In nonmetastatic rare pelvic tumor patients, the outcome was found to be poorer than in those concerned by common histologies stratified by organ. A higher rate of relapse and the lowest median RFS were observed in bladder and prostatic cancers.

Potential clinically useful prognostic biomarkers in triple-negative breast cancer: preliminary results of a retrospective analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis, even in its early stages. In the absence of postoperative targeted treatments, intensive adjuvant chemotherapy regimens are proposed. For those favorable histologies, such as apocrine and adenoid cystic carcinoma, which frequently belong to TNBC, aggressive treatments are unnecessary. PATIENTS AND METHODS: We retrospectively analyzed 631 cases of breast cancer, primary operated curatively, and followed up at our institution for at least 36 months to identify the bio-markers assessable by immunohistochemistry, to be proposed as prognostic score for tailoring adjuvant treatment to TNBC patients. RESULTS: The triple-negative phenotype was found in 85 patients (13.5%). Over a mean followup of 55.7 months, relapses occurred in 106 patients (16.8%), of which 18 (2.8%) were TNBC. Recurrence was directly correlated with Ki67 and cytokeratin 5/6 (CK5/6) immunoreactivity in all breast cancer patients (P=0.005), but only marginally with CK5/6 and epithelial cadherin (E-cad) expression in TNBC patients (P=0.07). Mean event-free survival (EFS) in TNBC patients was 85.52 months compared with 100.4 months in non-TNBC patients (P=0.228). The EFS of CK5/6-negative triple-negative patients was 68.84 months compared with 98.84 months in those who were CK5/6 positive (HR =5.08; P=0.038). EFS differed among patients identified as double-positive for E-cad and CK5/6 (83.87 months), those expressing E-cad or CK5/6 (64.23 months), and those negative for both biomarkers (39.64 months). CONCLUSION: These preliminary results suggest that CK5/6 and E-cad are possible core biomarkers for a cost-effective prognostic evaluation of primary operable TNBC patients.

Distant Oncologic Outcome of Patients with Locally Advanced Unresectable and Metastatic Esophageal Cancer after Multimodality Treatment.

Background: Combined modality therapy has been employed for the treatment of choice for locally advanced esophageal and eso-gastric junction cancers all around the globe but a unanimous consensus is missing. Methods: Medical files of 132 patients with confirmed locally advanced un-resectable, and metastatic esophageal cancer who presented to our center between 2010-2015 were retrospectively reviewed. Multimodality treatment consisting of chemo-radiotherapy or chemotherapy or radiotherapy alone and surgery in patients who convert to operability was planned according to tumor extend and performance status of the patient. Results: Seventy seven percent of the patient presented with squamous carcinoma and 23 % were adenocarcinoma. At the diagnosis 22 patients (16.6%) were stage IV. Concurrent chemoradiotherapy was administered in 26 patients (19.7%), chemotherapy in 91 patients (68.9%), radiotherapy in 83 patients (62.9%). After combined treatment, surgery with radical intent was possible in 21 patients (15.9%). After a follow up of 17.3 months, overall survival (OS) was 12 months, with one and two-year survival rate of 49.2% and 17.4%. In metastatic patients OS was 10 months. Patients who were converted to operability had a OS of 20 months vs. 10 months in patients who doesn't undergo surgery (p=0.002). Chemo-radiotherapy was superior in terms of OS compare with chemotherapy or radiotherapy administered sequential (17 vs. 10 months, p=0.013). Conclusions: Multimodality treatment in locally advanced esophageal cancers (concurrent radiochemotherapy followed by surgery) can be considered superior to each method as single therapy and radiotherapy and chemotherapy can make certain locally advanced esophageal tumors resectable.

Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma.

Gastric cancer is one of the most common types of cancer in the world, usually diagnosed at an advanced stage. Despite the advances in specific anticancer agents' development, the survival rates remain modest, even in early stages. In 15%-20% of cases, the human epidermal growth factor receptor 2 (HER2) overexpression was identified. We conducted a general review to summarize the progress that has been made in the targeted treatment of HER2-positive esogastric junction or gastric adenocarcinoma. According to our findings, trastuzumab is the only validated anti-HER2 agent in locally advanced or metastatic disease and its adjuvant effectiveness is assessed in a RTOG phase III study. In a previously treated advanced disease, the maytansine derivate TDM 1 failed to be approved as a second-line regimen, and the tyrosine kinase inhibitor, lapatinib, shows modest results. The antiangiogenics have not been analyzed in specific populations and targeting the mesenchymal-epithelial transition factor (MET) receptor, overexpressed in up to 46% of the advanced disease, seems encouraging. Regarding the checkpoint inhibitors, based on KEYNOTE 059 multilevel ongoing trial, stratified according to the HER2 and programmed death-ligand (PD-L) 1 status, pembrolizumab was approved for third-line treatment of gastric or gastroesophageal junction adenocarcinoma.