Locally advanced rectal cancer:The importance of a multidisciplinary approach

Rectal cancer accounts for a relevant part of colorectal cancer cases,with a mortality of 4-10/100000 per year.The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients.In the last two decades,new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival.Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates.The employment of neoadjuvant treatment,delivered before surgery,also achieved an improved local control and an increasedsphincter preservation rate in low-lying tumors,with an acceptable acute and late toxicity.This review describes the multidisciplinary management of rectal cancer,focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

Medical treatment for gastro-entero-pancreatic neuroendocrine tumours

Gastro-entero-pancreatic neuroendocrine neoplasms(GEPNENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor(VEGF), basic-fibroblastic growth factor, transforming growth factor(TGF-α and-β), platelet derived growth factor(PDGF), insulin-like growth factor-1(IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit(stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.

New findings on thymic epithelial tumors:Something is changing

Thymic epithelial tumors(TETs) are uncommon neoplasms with a wide range of anatomical, clinical, histological and molecular malignant entities. To date the management of TETs within clinical practice is based on a multimodal therapeutic strategy including surgery, chemotherapy and radiotherapy with a multidisciplinary approach and prognostic evaluation is mainly based on Masaoka staging and World Health Organization classification. Therefore novel strategies are needed, especially for refractory and/or recurrent TETs and for thymic carcinomas that present a poor prognosis. Personalized approaches are currely being developed and molecular targets are emerging from recent integrated genomic analyses. Targeted therapy will represent an important treatment option for TETs with an aggressive histology. To date, data indicate that vascular endothelial growth factor molecules, insulinlike growth factor 1 receptor, cyclin-dependent kinases and mammalian target of rapamycin may be potentially useful as targeted biological therapies.

Medical therapy for advanced gastro-entero-pancreatic and bronchopulmonary neuroendocrine tumors

Neuroendocrine tumors(NETs)represent a spectrum of rare neoplasms arising in different organism sites.Depending on the site of onset,they also can be distinguished using lab exams(secreting vs.nonsecreting),clinical symptoms(functioning vs.nonfunctioning),behavioral,morphological characteristics(tumor cells’architectural growth patterns,mitotic and Ki-67 index,presence of necrosis),and grade of cellular differentiation.The aim of this review is to focus on the main signaling pathways targeted by medical treatments of advanced sporadic gastro-entero-pancreatic(GEP)and bronchopulmonary(BP)neuroendocrine neoplasms.The scientific literature regarding treatment of advanced GEP and BP-NETs has been extensively reviewed using MEDLINE and PubMed databases,selecting principal and more recent research articles,clinical trials,and updated guidelines.Somatostatin analogues represent a valid approach to control symptoms in functioning tumors and to inhibit tumor progression in certain categories on the basis of the typical somatostatin receptor expression observed in NETs.The pathogenesis of NETs has been the subject of increased interest in recent years.Many driver mutations pathway genes have been identified as important factors in the carcinogenesis process and,therefore,as potential targets for new anticancer therapies.Activating mutations have been shown in epidermal growth factor receptor,stem cell factor receptor,platelet-derived growth factor receptor,vascular endothelial growth factor,basic-fibroblastic growth factor,transforming growth factor,insulin-like growth factor-1,and their receptors.Effective M-Tor inhibition pathway modulation has led to the approval of drugs in this field such as everolimus.New drugs and several combination regimens with targeted and newer biological agents are being developed and tested in recently conducted and ongoing trials.

Squamous cell carcinoma of the lung: clinical criteria for treatment strategy

Aim:Primary lung cancer is the leading cause of human cancer deaths worldwide,and squamous cell carcinoma(SCC)is one of the most frequent histologic subtypes.The aim of our study was to analyze clinical factors potentially affecting the overall outcome of advanced lung SCC patients.Methods:A series of 72 consecutive patients with advanced SCC undergoing chemotherapy at our institution between January 2007 and July 2013 were eligible for our analysis.Results:By univariate analysis,a better overall survival(OS)was related to response to first-line chemotherapy:median OS were 19.7 vs.7.17 months,respectively,for responders and nonresponders patients(P<0.0001).Eastern Cooperative Oncology Group performance status,gender,and surgery were other prognostic factors.No signifi cant relationship between OS and smoking status,age,body mass index,or type of treatment was found.In the third-line setting,a better OS was associated with objective response to second-line treatment(P=0.015).Conclusion:Our results suggest that differences in OS seem strictly associated with clinical response to previous treatments.These data should be considered in the therapeutic strategy and management of patients with SCC of the lung.

Electrolyte disorders in cancer patients: a systematic review

Electrolyte disorders are very common complications in cancer patients. They might be associated to a worsening outcome, influencing quality of life, possibility to receive anticancer drugs, and conditioning survival. In fact, they might provoke important morbidity, with dysfunction of multiple organs and rarely causing life-threatening conditions. Moreover, recent studies showed that they might worsen cancer patients' outcome, while a prompt correction seems to have a positive impact. Furthermore, there is evidence of a correlation between electrolyte alterations and poorer performance status, delays in therapy commencement and continuation, and negative treatment outcomes. These alterations usually involve sodium, potassium, calcium, and magnesium serum levels. Several causes might contribute to electrolyte disorders in cancer patients: cancer effects, such as paraneoplastic syndrome of inappropriate antidiuresis and tumor lysis syndrome;anti-cancer therapies;and other concomitant clinical conditions or treatments. However, the origin of the electrolyte disorder is often multifactorial, thus identifying and correcting the causes is not always feasible. Furthermore, they are often not recognized or not considered in clinical practice, worsening these alterations and patient condition. An improvement of knowledge about the physiological mechanisms underlying electrolyte disorders is necessary to strengthen their identification and set up a prompt, adequate, and effective treatment. The aim of this systematic review is to provide an analysis of the pathophysiological mechanisms of electrolyte abnormalities in cancer patients to facilitate their identification, management, and therapy to improve patient outcome.