Background: Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Methods: Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results: CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 10³ dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 10⁵ monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). Conclusions: We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix.

In recent years, the treatment of locally-advanced and metastatic cervical cancer has improved greatly due to the introduction of targeted therapies, new chemotherapy combinations, and emerging treatments. Candidates for potentially curative treatment are those patients with good functional status without associated comorbidities. Numerous trials have demonstrated that chemotherapy prolongs survival versus supportive care alone. In addition, polychemotherapy schemes are superior to single agent regimens. Targeted molecular agents have proven beneficial in the treatment of cervical cancer. Second-line treatment should be considered standard practice in patients with good functional status. Finally, given the poor survival outcomes in patients with metastatic disease, participation in clinical studies should always be considered the best option.

Aim: To evaluate the dose distribution to the left anterior descending (LAD) coronary artery in patients treated with postoperative three-dimensional conformal radiotherapy (3DCRT). Background: Postoperative radiotherapy may increase the risk of heart disease, particularly in patients with left-sided breast cancer. Clinical data on doses to the LAD are limited. Materials and methods: Retrospective study of 14 patients who underwent postoperative 3DCRT for left breast cancer in 2014. All data were retrieved from medical records. Means, medians, ranges, and percentages were calculated. Results: The mean dose to the LAD in patients with V25 < 1% was 0.12 cGy. D-mean, D-max and V25 to the heart were, respectively, 3.7 Gy (range, 0.9-4.18), 40.3 Gy (9.28-62.9), and 1.59 cGy. The mean D-mean and D-max values in the sample were 9.71 Gy and 33.2 Gy, respectively. The maximum dose to the LAD (D2%) ranged from 3.66 to 53.01 Gy. Due to the spacing of the CT slices (5 mm), it was not possible to completely contour the entire artery. The mean dose to the heart (3.3 Gy) was considered acceptable. Conclusions: The maximum dose to the LAD was as high as 53 Gy, suggesting an increased risk of cardiac morbidity. This study underscores the value of contouring the LAD and the value of the breath hold technique to reduce maximum cardiac doses. Smaller CT cuts (2.5 mm) can improve contouring. Larger studies with long-term follow up are needed to determine the radiation tolerance dose for the LAD. (C) 2018 Greater Poland Cancer Centre. Published by Elsevier Sp. z o.o. All rights reserved.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery—oral cavity, Clinical oncology—oral cavity, Head and neck surgery—oropharynx, Clinical oncology—oropharynx, Head and neck surgery—larynx, Head and neck surgery—larynx/hypopharynx, Clinical oncology—larynx/hypopharynx, Clinical oncology—recurrent and metastatic head and neck cancer, Head and neck surgery—reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

This survey is performed to learn about the structure of radiotherapy in México. Radiation oncology practice is increasing because of the higher incidence of cancer. There is no published data about radiotherapy in México. A questionnaire was sent to the 83 registered centers in the database of the Mexican regulatory agency. One out of the 32 states has no radiotherapy. 27 centers from 14 states provided their answers. 829 patients are treated annually with any radiotherapy modality in each center. Two centers have one cobalt machine, 7 have a cobalt and a linac and 10 have more than one linac. Five centers use 2D planning systems, 22 use 3D; 9, conventional simulators; 22, CT based simulation, and 1 center has no simulation. Most of the centers verify beams with films, electronic portal image devices and cone beam CTs are also used. Intensity modulated and image guided radiotherapy are performed in 5 states. Breast, prostate, cervix, lung, rectum and head and neck cancer are the six most common locations. There are 45 public and 38 private centers, 2 dedicated to children. Two gamma knife units, 5 Novalis systems, 1 tomotherapy and 2 cyberknife machines are working. All centers have at least one radiation oncologist, one physicist and one radiotherapist. Definitive conclusions cannot be drawn from this limited feedback due to a low participation of centers. This survey about radiotherapy in Mexico shows the heterogeneity of equipment as well as medical and technical staff in the whole country.

The current standard of care for locally advanced cervical cancer is whole pelvis and para-aortic radiation when indicated, delivered concomitantly with chemotherapy and brachytherapy. Para-aortic node involvement is a predictor of survival in locally advanced disease but presence of metastases is difficult to determine because the currently available imaging methods lack enough sensitivity to be able to detect accurately para-aortic metastases when surgical staging is not feasible. The objective of this review is to describe the current status of para-aortic lymph node irradiation in locally advanced cervical cancer. It includes analysis of the diagnostic imaging and surgical approaches for assessment of para-aortic lymph node dissemination, together with indications for radiotherapy and radiotherapeutic techniques.