Clinical and Translational Oncology

Endometrial cancer (EC) is the most common gynaecological tumour in developing countries. Most patients with EC are diagnosed at an early stage with a low risk of relapse and overall survival at 5 years greater than 85%. Nevertheless, there is a subgroup of patients with a very poor prognosis due to the pathological features and molecular characteristics. Until now there has been no consensus regarding adjuvant treatment in EC patients, with many open questions: In which patients is it indicated? Which is the best approach: chemotherapy, radiotherapy or both? What is the right timing? Relevant clinical trials are in progress in order to answer these questions. Unfortunately, the survival of patients with metastatic or recurrent EC is quite short due to the poor responses to standard first-line chemotherapy and the lack of second lines of treatment.

Soft tissue sarcomas are a heterogeneous group of rare tumours of mesenchymal origin. Evidence mapping is one of the most didactic and friendly approaches to organise and summarise the range of research activity in broad topic fields. The objective of this evidence mapping is to identify, describe and organise the current available evidence about therapeutic interventions on soft tissues sarcomas. We followed the methodology of global evidence mapping. We performed a search of the PubMed, EMBASE, The Cochrane Library and Epistemonikos to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two independent literature reviewers assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and used tables and a bubble plot to display the results. The map is based on 24 SRs that met eligibility criteria and included 66 individual studies. Three-quarters were either observational or uncontrolled clinical trials. The quality of the included SRs was in general moderate or high. We identified 64 PICO questions from them. The corresponding results mostly favoured the intervention arm. This evidence mapping was built on the basis of SRs, which mostly included non-experimental studies and were qualified by the AMSTAR tool as of moderate quality. The evidence mapping created from PICO questions is a useful approach to describe complex and huge clinical topics through graphical media and orientate further research to fulfil the existing gaps. However, it is important to delimitate the steps of the evidence mapping in a pre-established protocol.

Trastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the clinicopathologic factors that predict the outcome of routine trastuzumab therapy remain unclear. The outcome and safety profile of trastuzumab therapy in untreated HER2 positive AGC was evaluated in this prospective observational study. Clinical and pathological data including demographics, treatment profiles, expression level of HER2 were analyzed to identify predictive factors of trastuzumab-based first-line therapy for their progression-free survival (PFS). Overall, 107 patients were eligible. The median number of treatment cycles was 9 (range 1–44), the median PFS and median overall survival (OS) were 7.7 months (95% CI 6.5–8.9) and 16.0 months (95% CI 13.2–18.8), respectively. The confirmed response rate was 58.9%, and the disease control rate was 82.2%. Patients with liver metastasis (HR 1.616) and poor performance status (PS, HR 2.518) were independently associated with a worse PFS, while the other clinicopathological factors including demographics, treatment profiles and some other clinical characteristics did not predict the survival. In routine clinical practice, the addition of trastuzumab to chemotherapy was effective and safe in real-world setting in Chinese patients with HER2 positive AGC, regardless of most of the clinicopathological factors. Further studies are needed to improve the prognosis of HER2 positive patients with liver metastasis or poor PS. Trial Registration clinicaltrials.gov Identifier: NCT03024450

To compare the differences between 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) with traditional after-loading radiotherapy in aspects of efficacies and side effects. MTT assay was adopted to detect the inhibitive effects of 5-ALA-PDT on Hela cells proliferation. Flow cytometry was used to analyze cell apoptosis. After establishment of human cervical cancer xenograft model, the comparisons between 5-ALA-PDT with radiotherapy were performed with respect to treatment efficacies (survival rate, body weight, and tumor volume) and side effects (appearance and behavior, ovarian endocrine functions, and skin lesion around the tumor). 5-Aminolevulinic acid photodynamic therapy exerted killing effects on cervical cancer cells. Morphological changes and flow cytometric analyses indicated apoptosis to be one of the mechanisms for tumor growth suppression. Both proliferation inhibition and cell apoptosis showed dependency on photosensitizer concentration and irradiation intensity. Repeated photodynamic therapy presented stronger inhibitive effects on tumor growth compared to after-loading radiotherapy, while producing milder impairment of ovarian endocrine functions and skin lesions around the tumors. 5-Aminolevulinic acid photodynamic therapy has great potential to be an alternative treatment modality for cervical cancer.

Breast cancer is the most common cancer and the main cause of cancer morbidity for women worldwide and is manifestation of abnormal genetic as well as epigenetic changes. Therefore, our aim was to study the association of BRCA1 promoter methylation with rs11655505 (c.−2265C/T) variants and gene expression in sporadic breast cancer. Twenty-nine sporadic breast cancer tissues and 26 normal biopsies were used for this study. Genomic DNA and total RNA were extracted from paraffin-embedded tissue and SNP analysis performed. Methylation status of the BRCA1 promoter region was determined by methylation-specific PCR after sodium bisulfite modification of DNA. Among all clinical–pathological parameters only estrogen receptor –ve and +ve samples were significantly different for methylation status (P = 0.04). The genotypic (CC, CT and TT), allelic frequencies and methylation status had not been found to be significantly different from that of healthy controls (P = 0.67, 0.71 and 0.17, respectively). Similarly, methylated BRCA1 promoter was not found to be significantly different in different genotypes from unmethylated promoters between patients and controls. Interestingly, only heterozygous (CT) genotypes with low and normal expression of BRCA1 were significantly different for the differential expression of BRCA1 compared to controls (P = 0.004). However, in tumor samples decreased expression of gene is associated with methylated state of BRCA1 promoter [OR (95 % CI) = 25.09 (2.17–29.75); P = 0.01]. Our data suggest that both single nucleotide variations rs11655505 (c.–2265C/T) and the methylation status of BRCA1 are not associated significantly with the occurrence of sporadic breast cancer in studied population. However, decreased expression of gene is associated with the CT genotypes and the disease. But, in case of tumor samples, an association of methylation of the promoter to the decreased expression of BRCA1 gene suggests the possible role of methylation in gene silencing.

Sarcomas are low-incidence tumours, but their poor prognosis and complex treatment require the work of a multidisciplinary medical team. The Plastic Surgery Service forms part of the Sarcoma Functional Unit in our centre, performing tumour exeresis as well as immediate reconstruction. We present a retrospective study on the experience of the Plastic Surgery Service of the Hospital Universitario de Bellvitge in the treatment of 133 sarcomas over 20 years. The surgical treatment was based on local radical surgery supported by primary reconstructive surgery in 42.9% of the cases, with an amputation rate in limb sarcomas of 9.7%. Radiotherapy and chemotherapy were used in the high-grade sarcomas as adjuvant treatment. The anatomical location of the head and neck was associated with the need for reconstructive procedures. Survival free from local recurrence was 84.72% at 5 years. Disease-specific survival was 81.22% at 5 years. The only prognostic factor for survival in our series was histological grade. Primary reconstructive surgery has a fundamental role in sarcoma treatment enabling radical surgical resection, avoiding amputations and facilitating adjuvant treatments.