Ramona Vergés

Effects of probiotic Lactobacillus casei DN-114 001 in prevention of radiation-induced diarrhea: results from multicenter, randomized, placebo-controlled nutritional trial.

PURPOSE To determine whether a probiotic drink containing Lactobacillus casei DN-114 001 reduces the incidence of radiation-induced diarrhea in patients with gynecologic cancer. METHODS AND MATERIALS Patients who were undergoing pelvic radiotherapy (45-50 Gy, conventional fractionation) for either cervical carcinoma (radiotherapy and weekly cisplatin) or endometrial adenocarcinoma (postoperative radiotherapy) were randomly assigned to a probiotic drink or placebo, in a double-blind fashion. The probiotic drink consisted of liquid yogurt containing L. casei DN-114 001 at 10(8) CFU/g. The patients recorded the daily the number of bowel movements and scored the stool consistency using the Bristol scale. Diarrhea was graded weekly according the Common Toxicity Criteria system. The primary endpoint was to reduce the incidence of diarrhea, defined by a Common Toxicity Criteria Grade of 2 or greater or the need for loperamide. RESULTS A total of 85 patients were enrolled. Grade 2 or greater diarrhea and/or the use of loperamide was observed in 24 of 41 patients in the placebo group and 30 of 44 in the probiotic group (p = 0.568). No differences were found in the median time to the presentation of the primary endpoint. Probiotic intervention had a significant effect on stool consistency (p = 0.04). The median time for patients to present with Bristol scale stools of Type 6 or greater was 14 days for patients receiving the probiotic drink vs. 10 days for those receiving placebo. CONCLUSION Nutritional intervention with the probiotic drink containing L. casei DN-114 001 does not reduce the incidence of radiation-induced diarrhea as defined by a Common Toxicity Criteria Grade 2 or greater. However, it had a significant effect on stool consistency as measured by the Bristol scale.

Overexpression of Phosphorylated 4E-BP1 Predicts for Tumor Recurrence and Reduced Survival in Cervical Carcinoma Treated With Postoperative Radiotherapy

PURPOSE To examine the prognostic value of the 4E-BP1 activation state and related upstream/downstream signaling proteins on the clinical outcome of patients with intermediate- or high-risk early-stage cervical carcinoma treated with postoperative radiotherapy and to determine the optimal treatment of early-stage cervical carcinoma. METHODS AND MATERIALS Immunohistochemical staining was performed on 64 formalin-fixed, paraffin-embedded cervical carcinoma surgical specimens for each protein of the panel (p4E-BP1, phosphorylated mitogen-activated protein kinase, pAkt, vascular endothelial growth factor, KDR, Bcl-2, TP53, receptor for activated C-kinase 1). The expression patterns were related to the clinical data. All patients received postoperative radiotherapy. Concurrent chemotherapy was added if high-risk features were present. The median follow-up was 40 months. RESULTS Of the 64 patients, 13 received concomitant chemotherapy. p4E-BP1 overexpression in moderate/high-risk early-stage cervical carcinoma correlated significantly with disease-free survival (hazard ratio, 4.39; p = .009) and overall survival (hazard ratio, 4.88; p = .005). Vascular endothelial growth factor, and its receptor KDR, had positive immunoreactivity in all tumor samples. No correlation with clinical outcome was found for the remaining proteins evaluated. CONCLUSION In this study, moderate/high-risk early-stage cervical carcinoma with low p4E-BP1 expression was highly curable with the current postoperative treatments. For tumors with p4E-BP1 overexpression, new investigational strategies are needed.

Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS)

Soft tissue sarcomas (STS) constitute an uncommon and heterogeneous group of tumours, which require a complex and specialized multidisciplinary management. The diagnostic approach should include imaging studies and core needle biopsy performed prior to undertaking surgery. Wide excision is the mainstay of treatment for localized sarcoma, and associated preoperative or postoperative radiotherapy should be administered in high-risk patients. Adjuvant chemotherapy was associated with a modest improvement in survival in a meta-analysis and constitutes a standard option in selected patients with high-risk STS. In metastatic patients, surgery must be evaluated in selected cases. In the rest of patients, chemotherapy and, in some subtypes, targeted therapy often used in a sequential strategy constitutes the treatment of election. Despite important advances in the understanding of the pathophysiology of the disease, the advances achieved in therapeutic results may be deemed still insufficient. Moreover, due to the rarity and complexity of the disease, the results in clinical practice are not always optimal. For this reason, the Spanish Group for Research on Sarcoma (GEIS) has developed a multidisciplinary clinical practice guidelines document, with the aim of facilitating the diagnosis and treatment of these patients in Spain. In the document, each practical recommendation is accompanied by level of evidence and grade of recommendation on the basis of the available data.

New and safe experimental model of radiation-induced neurovascular histological changes for microsurgical research

The aim is to create a new and safe experimental model of radiation-induced neurovascular histological changes with reduced morbidity and mortality for use with experimental microsurgical techniques. Seventy-two Sprague–Dawley rats (250–300 g) were divided as follows: Group I: control group, 24 rats clinically evaluated during six weeks; Group II: evaluation of acute side-effects (two-week follow-up period), 24 irradiated (20 Gy) rats; and Group III: evaluation of subacute side-effects (six-week follow-up period), 24 irradiated (20 Gy) rats. Variables included clinical assessments, weight, vascular permeability (arterial and venous), mortality and histological studies. No significant differences were observed between groups with respect to the variables studied. Significant differences were observed between groups I vs II–III regarding survival rates and histological changes to arteries, veins and nerves. Rat body weights showed progressive increases in all groups, and the mortality rate of the present model is 10.4% compared with 30–40% in the previous models. In conclusion, the designed model induces selective changes by radiotherapy in the neurovascular bundle without histological changes affecting the surrounding tissues. This model allows therapeutic experimental studies to be conducted, including the viability of microvascular and microneural sutures post radiotherapy in the cervical neurovascular bundle.

Effect of Previous Irradiation on Vascular Thrombosis of Microsurgical Anastomosis: A Preclinical Study in Rats

Background: The objective of the present investigation was to compare the effect of neoadjuvant irradiation on the microvascular anastomosis in cervical bundle using an experimental model in rats. Methods: One hundred forty male Sprague–Dawley rats were allocated into 4 groups: group I, control, arterial microanastomosis; group II, control, venous microanastomosis; group III, arterial microanastomosis with previous irradiation (20 Gy); and group IV, venous microanastomosis with previous irradiation (20 Gy). Clinical parameters, technical values of anastomosis, patency, and histopathological parameters were evaluated. Results: Irradiated groups (III and IV) and vein anastomosis groups (II and IV) showed significantly increased technical difficulties. Group IV showed significantly reduced patency rates (7/35) when compared with the control group (0/35). Radiotherapy significantly decreased the patency rates of the vein (7/35) when compared with the artery (1/35). Groups III and IV showed significantly reduced number of endothelial cells and also showed the presence of intimal thickening and adventitial fibrosis as compared with the control group. Conclusion: Neoadjuvant radiotherapy reduces the viability of the venous anastomosis in a preclinical rat model with a significant increase in the incidence of vein thrombosis.

926PIMPACT OF DEMOGRAPHIC CHARACTERISTICS, STAGING METHODS AND TREATMENT IN A EUROPEAN LOCALLY ADVANCED CERVICAL CANCER (LACC) POPULATION

ABSTRACT Aim: FIGO defines Cervical Cancer staging but in developed countries Pelvic MRI, PET/CT and surgical staging (SxS) are widely used. LACC standard of care is chemoradiotherapy (CTRT). Besides FIGO stage and Lymph nodes (LN) status, other prognostic factors (PF) are trying to be identified. Methods: Between May 2008 and November 2013, 148 consecutive LACC patients (pts) treated homogenously with CTRT from 2 Spanish academic Institutions were collected. Demographic, social, clinical characteristics and staging methods were analyzed and correlated with clinical outcomes. Results: Median age at diagnosis was 51.8 years (23-82.5) and PS 0-1(98%). Sixty-five percent had not followed screening program, 55% had a postmenopausal status, 58% never smokers. Median time from first symptom to diagnosis was 2.9 months (0- 58.3). Squamous cell 79.1%; G3 36.3%; High risk HPV 91.8%. FIGO Stage: IB2 8.8%; IIA 10.8%; IIB 48%; IIIB 17.6%; IVA 4.1% . MRI, PET/CT or both were performed in 95.3%, 51.7%, and 48.6% respectively. Clinical and MRI Stage correlation was: IB2 30.8%; IIB 76.1%; IIIB 19.2% and IVA 83.3%. Para-Aortic (PA) LN were studied by PET/CT, SxS and both in 51.7%, 50.7% and 33.1% respectively. In the combined group, negative PA LN were: 91.8% by PET/CT and 87.8% by SxS, showing a PET/CT specificity of 93%. All pts received Pelvic EBRT (median 45Gy) through 3D (81.8%) and IMRT (18.2%) concurrent with 6 weekly cisplatin (1-7). PA field and parametrial boost was added in 23% and 53.4% respectively. PDR Brachytherapy was delivered in 79.1%. Planned treatment was completed in 74.3%; median duration 8.5 weeks (3.8-18.8). Median follow-up was 22.4 months (2.3-61.2). RFS and OS at 2 years: 71.4%; 95%IC (63.4%-79%) and 80.7%; 95%IC (73.6%-88%) respectively. In univariate analysis OS main PF was FIGO Stage: IB2 92,3%, IIA 87.5%, IIB 81.7%, IIIB 65.4%, IVA 66.7%. Smoking does not impact in OS; oral anticonception and pre-menopausal status showed a trend to worse OS. Conclusions: CTRT is still an insufficient treatment in LACC. FIGO Staging might be improved adding imaging tests. PA Lymph nodes diagnostic method is still matter of controversy; our PET/CT data are according to literature. Neither social nor demographic characteristics were identified as PF. Disclosure: All authors have declared no conflicts of interest.