A djuvant treatment in patients at high risk of recurrence of thymoma: Efficacy and safety of a three-dimensional conformal radiation therapy regimen

The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. METHODS: Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. RESULTS: Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. CONCLUSION: Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma

New biomolecular prognostic and predictive factors of response to treatment in colo-rectal cancer

microRNAs are small single-stranded RNA molecules of approximately 22 nucleotides that function as post-transcriptional gene regulators. MiRNAs play important roles in the control of many biological processes, such as cellular development, differentiation, proliferation, apoptosis and metabolism. miRNA expression is aberrant in several human tumors. The biologic roles of miRNAs in cancer suggest a correlation with prognosis and therapeutic outcome. In our study, we examined by microarray the expression of 939 miRNArole in fresh biopsies of 39 patients affected by local advanced rectal cancer, treated with neoadjuvant chemoradiotherapy and surgery, with the aim to investigate the possible predictive and prognostic role. We have identified 14 miRNA which correlate significantly with Tumor Regression Grade 1. Our results suggest that miRNA expression profile could have relevance as prognostic and predictive factor of response to chemo-radiotherapy in colo-rectal cancer

Anaplastic thyroid carcinoma: A comprehensive review of current and future therapeutic options

Anaplastic thyroid carcinoma (ATC) is the rarest, but deadliest histologic type among thyroid malignancies, with a dismal median survival of 3-9 mo. Even though ATC accounts for less than 2% of all thyroid tumors, it is responsible for 14%-39% of thyroid carcinoma-related deaths. ATC clinically presents as a rapidly growing mass in the neck, associated with dyspnoea, dysphagia and vocal cord paralysis. It is usually locally advanced and often metastatic at initial presentation. For operable diseases, the combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin and cisplatin, is the best treatment strategy. Cytotoxic drugs for advanced/metastatic ATC are poorly effective. On the other hand, targeted agents might represent a viable therapeutic option. Axitinib, combretastatin A4, sorafenib and imatinib have been tested in small clinical trials of ATC, with a promising disease control rate ranging from 33% to 75%. Other clinical trials of targeted therapy for thyroid carcinoma are currently ongoing. Biological agents that are under investigation include pazopanib, gefitinib and everolimus. With the very limited therapeutic armamentarium available at the present time, targeted therapy constitutes an exciting new horizon for ATC. In future, biological agents will probably represent the standard of care for this aggressive malignancy, in the same fashion as it has recently occurred for other chemo-refractory tumors, such as kidney and hepatic cancer

Locally advanced nasopharyngeal carcinoma: Current and emerging treatment strategies

Although nasopharyngeal carcinoma (NPC) is a widespread malignant tumor, it is particularly frequent in Southeast Asia. Although T1 tumors can be effectively controlled with exclusive radiotherapy, this treatment modality is insufficient for most NPC patients, who present with locally advanced disease at diagnosis. In fact, for stages ranging from T2b N0 to T4 N3, definitive scientific evidence supports the use of concurrent platinum-based chemotherapy with standard external beam radiotherapy. This treatment approach has shown a statistically significant advantage in terms of overall survival, with respect to radiotherapy alone. Several trials have also investigated the use of neoadjuvant and adjuvant chemotherapy in combination with radiotherapy or chemo-radiotherapy. Platinum compounds, anthracyclines and taxanes are among the chemotherapy agents employed. This review focuses on the clinical results obtained in the field of adjuvant/concurrent/neoadjuvant chemotherapy for locally advanced NPC, for which exclusive concurrent chemo-radiotherapy currently represents the standard treatment approach

Ipilimumab in the treatment of metastatic melanoma: management of adverse events

Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTLA-4 inhibitory signal, allowing the immune system to react to cancer cells. Due to its immune-based mechanism of action, ipilimumab causes the inhibition of CTLA-4-mediated immunomodulatory effects, the enhancement of antitumor specific immune response mediated by the weakening of self-tolerance mechanisms while exacerbating the development of autoimmune diseases and immune-related adverse events, including dermatitis, hepatitis, enterocolitis, hypophysitis, and uveitis

Epstein-Barr virus infection and nasopharyngeal carcinoma: The other side of the coin

Oncogenic viruses may have a significant impact on the therapeutic management of several malignancies besides their well-known role in tumor pathogenesis. Epstein-Barr virus (EBV) induces neoplastic transformation of epithelial cells of the nasopharynx by various molecular mechanisms mostly involving activation of oncogenes and inactivation of tumor-suppressor genes. EBV infection can also induce the expression of several immunogenic peptides on the plasma membrane of the infected cells. Importantly, these virus-related antigens may be used as targets for antitumor immunotherapy-based treatment strategies. Two different immunotherapy strategies, namely adoptive and active immunotherapy, have been developed and strongly improved in the recent years. Furthermore, EBV infection may influence the use of targeted therapies for nasopharyngeal carcinoma (NPC) considering that the presence of EBV can induce important modifications in cell signaling. As an example, latent membrane protein type 1 is a viral transmembrane protein mainly involved in the cancerogenesis process, which can also mediate overexpression of the epidermal growth factor receptor (EGFR) in NPC cells, rendering them more sensitive to anti-EGFR therapy. Finally, EBV may induce epigenetic changes in the infected cells, such as DNA hypermethylation and histone deacetylation, that can sustain tumor growth and can thus be considered potential targets for novel therapies. In conclusion, EBV infection can modify important biological features of NPC cells, rendering them more vulnerable to both immunotherapy and targeted therapy

Translational Insights and New Therapeutic Perspectives in Head and Neck Tumors

Head and neck squamous cell carcinoma (HNSCC) is characterized by a high mortality rate owing to very few available oncological treatments. For many years, a combination of platinum-based chemotherapy and anti-EGFR antibody cetuximab has represented the only available option for first-line therapy. Recently, immunotherapy has been presented an alternative for positive PD-L1 HNSCC. However, the oncologists’ community foresees that a new therapeutic era is approaching. In fact, no-chemo options and some molecular targets are on the horizon. This narrative review addresses past, present, and future therapeutic options for HNSCC from a translational point of view

Thyroid cancer management: From a suspicious nodule to targeted therapy

Thyroid nodules are very common, and their frequency is four to five times higher in women than in men. Most of them are benign, with only a very little percentage revealing a malignant neoplasm. About 50% of thyroid nodules are detected by self-palpation of neck, whereas the other 50% are diagnosed by neck ultrasonography and following fine-needle aspiration. Management of thyroid nodules is very difficult, because benign nodules are prevalent, whereas thyroid carcinoma is uncommon, representing only 1% of all malignancies. A standard diagnostic approach is represented by 'first-level' exams, consisting in neck ultrasonography and serum thyroid-stimulating hormone measurement, followed, only for nodules that are suspicious of malignancy, by 'second-level' exams, consisting of fine-needle aspiration and mutational test, which does detect particular DNA mutations present only in malignant cells. In this review, we will analyze the genetics of thyroid cancer and its heterogeneity, and we will briefly describe the current available diagnostic and therapeutic approaches

MELANOMA ADJUVANT TREATMENT: current insight and clinical features

Melanoma represents 2-3% of all cancers, 95% of them arise from skin, while only 5% are non-cutaneous melanoma. Despite an optimal surgery management, the risk of a local and systemic relapse remains high, particularly in high-risk patients (node-positive or node-negative T3b, T4 a/b). We conducted a systematic review of the main published and ongoing phase I/II/III trials between 2000 and June 2015 on the adjuvant treatment of cutaneous melanoma. The IFN remains the only option currently available for this aim. Ipilimumab represents a possible breakthrough in this setting, considering the positive results of the EORTC 18701 trials in terms of disease free survival (DFS), while data regarding OS are pending. Recent advances in the understanding of the biology of melanoma result in the identification of MAPK pathway role in the melanoma development Based on these features, B-RAF inhibitors and their combination with immunotherapy could represent the upcoming therapeutic strategy