SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

OBJECTIVE: This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS: Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. RESULTS: A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100 Gy was delivered to all lesions. With a median follow-up of 23.1 months (range: 13.4-30.9 months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48 months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8 months, respectively. The actuarial median overall survival (OS) was 27.7 months from SBRT and 52.5 months from metastases diagnosis. Patients with lesion diameter ≤ 5 cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. CONCLUSIONS: This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

Characterizing Cleft Rhinoplasty Across Skeletal Maturity: A Systematic Review of Terminology and Surgical Techniques.

OBJECTIVE: The purpose of this study is to assess cleft rhinoplasty terminology across phases of growth.Design/Setting: A systematic review was performed on cleft rhinoplasty publications over 20 years.Interventions: Studies were categorized by age at surgical intervention: infant (<1 year); immature (1 to 14 years); mature (>15 years).Main Outcome Measures: Collected data included terminology used and surgical techniques. RESULTS: The 288 studies included demonstrated a wide range of terminology. In the infant group, 51/54 studies used the term "primary." In the immature group, 7/18 studies used the term "primary," 3/18 used "secondary." In the mature group, 2/33 studies used the term "primary," 16/33 used "secondary," 2/33 used "definitive," 5/33 used terms such as "mature," "adult," and "late," and 8/33 did not use terminology.Surgical technique assessment demonstrated: cleft rhinoplasty at infancy used nostril rim or no nasal incision, immature rhinoplasty used closed and open rhinoplasty incisions; and mature rhinoplasty used a majority of open rhinoplasty. Infant and immature cleft rhinoplasty incorporated septal harvest or spur removal in <10% of cases, whereas these procedures were common in mature rhinoplasty. No studies in infants or immature patients used osteotomies or septal grafts, common techniques in mature rhinoplasty. CONCLUSIONS: Current terminology for cleft rhinoplasty is varied and inconsistently applied across stages of facial development. However, cleft rhinoplasty performed at infancy, childhood, and facial maturity are surgically distinct procedures. The authors recommend the terminology "infant," "immature," and "mature" cleft rhinoplasty to accurately describe this procedure within the context of skeletal growth.

Utility of CYP2D6 copy number variants as prognostic biomarker in localized anal squamous cell carcinoma.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes. METHODS: Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors. RESULTS: On the discovery cohort, the median age was 61 years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33 months, and overall survival was 45 months. Twenty-nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5 years than those with two CYP2D6 copies (21% vs. 84%; p < .0002, hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.7-24.9). In the GEMCAD validation cohort, patients with CYP2D6 CNV also had worse DFS at 5 years (56% vs. 87%; p = .02, HR = 3.6; 95% CI, 1.1-5.7). Mitochondria and mitochondrial cell-cycle proteins were overexpressed in patients with CYP2D6 CNV. CONCLUSIONS: Tumor CYP2D6 CNV identified patients with a significantly worse DFS at 5 years among localized ASCC patients treated with 5-fluorouracil, mitomycin C, and radiotherapy. Proteomics pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets for these high-risk patients. PLAIN LANGUAGE SUMMARY: Anal squamous cell carcinoma is an infrequent tumor whose treatment has not been changed since the 1970s. However, disease-free survival in late staged tumors is between 40% and 70%. The presence of an alteration in the number of copies of CYP2D6 gene is a biomarker of worse disease-free survival. The analysis of the proteins in these high-risk patients pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets. Therefore, the determination of the number of copies of CYP2D6 allows the identification of anal squamous carcinoma patients with a high-risk of relapse that could be redirected to a clinical trial. Additionally, this study may be useful to suggest new treatment strategies to increase current therapy efficacy.

"Septoplasty" Performed at Primary Cleft Rhinoplasty: A Systematic Review of Techniques and Call for Accurate Terminology.

OBJECTIVE: Primary cleft nasal repair can include septal reconstruction. We hypothesize that primary cleft septoplasty and adult septoplasty have fundamental differences that render these procedures as distinct surgical entities. DESIGN: Systematic review of the PubMed, Cochrane, and Embase databases performed on pediatric cleft and general adult septoplasty techniques through December 2021. (PROSPERO ID CRD42022295763). MAIN OUTCOME MEASURES: Collected data included information on septal dissection, septal detachment, and management of the bony and cartilaginous septum. RESULTS: Twenty-eight pediatric cleft septoplasty and 229 adult septoplasty studies were included. Dissection in primary cleft septoplasty was limited to the anterocaudal septum, while secondary cleft septoplasty and adult septoplasty techniques entailed wide exposures of the cartilaginous septum with or without exposure of the perpendicular plate of the ethmoid. In primary cleft septoplasty, detachment of the septum was mostly limited to the nasal spine and anterior base of the cartilaginous septum, while secondary cleft septoplasty and adult septoplasty included detachment from the vomer, and ethmoid. In the few reports of cartilage excision during primary cleft septoplasty, removal was limited to the anterior inferior border of the septum, while secondary cleft septoplasty and adult septoplasty included excision of the cartilaginous and bony septum. CONCLUSION: Primary cleft septoplasty is distinct from septoplasty performed on facially mature patients. More specifically, septal dissection and detachment are limited to the anterior caudal area during primary lip repair, with rare removal of cartilage or bone. Given these differences, the authors suggest the term "septal reset" to describe septoplasty performed during primary cleft nasal repair.

The Effect of Public Healthcare Expenditure on the Reduction in Mortality Rates Caused by Unhealthy Habits among the Population.

The health systems of developed countries aim to reduce the mortality rates of their populations. To this end, they must fight against the unhealthy habits of citizens, such as smoking, excessive alcohol consumption, and sedentarism, since these result in a large number of deaths each year. Our research aims to analyze whether an increase in health resources influences the number of deaths caused by the unhealthy habits of the population. To achieve this objective, a sample containing key indicators of the Spanish health system was analyzed using the partial least squares structural equation modeling (PLS-SEM) method. The results show how increasing public health spending and, thus, the resources allocated to healthcare can curb the adverse effects of the population's unhealthy habits. These results have important implications for theory and practice, demonstrating the need for adequate investment in the healthcare system to reduce mortality among the population.

SARS-CoV-2 pneumomediastinum. A proposed pneumomediastinum classification

Pneumomediastinum is a rare complication of viral pneumonias. However, as a result of the COVID-19 pandemic, the reports of SARS-CoV-2 related pneumomediastinum have increased. This type of pneumomediastinum is known as "spontaneous" pneumomediastinum. Spontaneous pneumomediastinum is defined as the presence of air in the mediastinal cavity with no apparent cause, but paradoxically, the group termed "spontaneous" is the one with the greatest trigger. Therefore, we believe that the current classification does not coincide with the definition. We present five SARS-CoV-2 pneumomediastinum cases and propose a pneumomediastinum classification. These are the first published reports in our country. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2252).

El neumomediastino es una complicación poco frecuente de las neumonías virales; sin embargo, a raíz de la pandemia de la COVID-19, los informes de casos de neumomediastino por SARS-CoV-2 se han incrementado. A este tipo de neumomediastino se le denomina espontáneo. Se define como neumomediastino espontáneo a la presencia de aire en la cavidad mediastínica sin ninguna causa aparente, pero paradójicamente, el grupo denominado espontáneo es el que tiene mayor causa desencadenante, por lo tanto, creemos que la clasificación actual no es coherente con el significado. Presentamos cinco casos de neumomediastino por SARS-CoV-2 y proponemos una clasificación para el neumomediastino. Estos son los primeros informes publicados en nuestro país. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2252).

Analyzing Spanish-Language Public Sentiment in the Context of a Pandemic and Social Unrest: The Panama Case.

Over the past decade, an increase in global connectivity and social media users has changed the way in which opinions and sentiments are shared. Platforms such as Twitter can act as public forums for expressing opinions on non-personal matters, but often also as an outlet for individuals to share their feelings and personal thoughts. This becomes especially evident during times of crisis, such as a massive civil disorder or a pandemic. This study proposes the estimation and analysis of sentiments expressed by Twitter users of the Republic of Panama during the years 2019 and 2020. The proposed workflow is comprised of the extraction, quantification, processing and analysis of Spanish-language Twitter data based on Sentiment Analysis. This case of study highlights the importance of developing natural language processing resources explicitly devised for supporting opinion mining applications in Latin American countries, where language regionalisms can drastically change the lexicon on each country. A comparative analysis performed between popular machine learning algorithms demonstrated that a version of a distributed gradient boosting algorithm could infer sentiment polarity contained in Spanish text in an accurate and time-effective manner. This algorithm is the tool used to analyze over 20 million tweets produced between the years of 2019 and 2020 by residents of the Republic of Panama, accurately displaying strong sentiment responses to events occurred in the country over the two years that the analysis performed spanned. The obtained results highlight the potential that methodologies such as the one proposed in this study could have for transparent government monitoring of responses to public policies on a population scale.

Síndrome hemolítico urémico atípico en lactantes con mutaciones genéticas: Reporte de 3 casos / Atypical hemolytic uremic syndrome (aHUS) in infants, with genetic mutations, about three cases

RESUMEN El síndrome hemolítico urémico atípico (SHUa) es una entidad clínica considerada rara; sin embargo, es la causa más común de insuficiencia renal aguda en niños. Esta enfermedad se acompaña de anemia hemolítica microangiopática, trombocitopenia, retención nitrogenada y afectación de la función renal, por lo que representa alta morbilidad y compromiso sistémico. Se reportan tres casos de SHUa en lactantes que presentaron pródromos respiratorios, diarrea, anemia hemolítica y trombocitopenia, con pérdida de función renal. Estos casos mostraron que dicha patología está asociada a mutaciones en los genes: CFH (Complemento Factor H), MCP (Membrana Cofactor Proteín), CFHR1 (Complemento Factor H-Related Proteín1), CFHR5 (Complemento factor H-Related Protein 5) y el gen C3 (Complemento component 3). Los genes CFH y MCP se encontraron afectados en dos de los casos, mientras que el tercer caso mostró una mutación nueva no reportada en el gen C3. Estos resultados evidencian que estas mutaciones están presentes en el Perú, por lo que se debe investigar y establecer medidas de prevención para reducir el alto riesgo de morbilidad y mortalidad que presentan los niños portadores SHUa.

SUMMARY The atypical hemolytic uremic syndrome (aHUS) is a rare clinical entity, but it is the most common cause of acute kidney failure in kids. The disease is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure, and it is associated with high morbidity and systemic involvement. We report here three cases of aHUS in infants presenting with prodromal respiratory symptoms, diarrhea, hemolytic anemia, thrombocytopenia and acute renal failure. aHUS cases depict mutations in several genes: membrane cofactor protein (MCP) and complement factor H related proteins 1 and 5 (CFH, RP1 and PR5. Two our patients showed mutations in the genes CFH and MCP, and one presented a new non-previously reported mutation in the gen C3. Our results emphasize the existence of these aHUS mutations and underscore the need to study them to prevent morbidity and mortality.

Pyrazinamide-isoniazid hybrid: synthesis optimisation, characterisation, and antituberculous activity / Híbrido pirazinamida-isoniacida: optimización de síntesis, caracterización y actividad antituberculosa / Híbrido pirazinamida-isoniazida: otimização da síntese, caracterização e atividade antituberculose

Abstract Over time, the effective resistance mechanisms to various first- and second-line drugs against the disease of tuberculosis make its treatment extremely difficult. This work presents a new approach to synthesizing a hybrid of antituberculosis medications: isoniazid (INH) and pyrazinamide (PZA). The synthesis was performed using ultrasound-assisted synthesis to obtain an overall yield of 70%, minimizing the reaction time from 7 to 1 h. The evaluation of the biological activity of the hybrid (compound 2) was tested using the tetrazolium microplate assay (TEMA), showing inhibition in the growth of Mycobacterium tuberculosis H37Rv at a concentration of 0.025 mM at pH 6.0 and 6.7.

Resumen Debido a los grandes mecanismos de resistencia a lo largo del tiempo de diversos fármacos de primera y segunda línea contra la enfermedad de la tuberculosis, el tratamiento sigue dificultándose. Este trabajo presenta un nuevo enfoque para sintetizar un híbrido de fármacos antituberculosos: isoniazida (INH) y pirazinamida (PZA). La síntesis fue asistida por ultrasonido con el fin de obtener un rendimiento global del 70%, minimizando el tiempo de reacción de 7 a ' h. La evaluación de la actividad biológica del híbrido (compuesto 2) se probó usando el ensayo de microplaca de tetrazolio (TEMA), que mostró una inhibición en el crecimiento de Mycobacterium tuberculosis H37Rv a una concentración de 0,025 mM a pH 6,0 y 6,7.

Resumo Devido aos grandes mecanismos de resistência ao longo do tempo a diversos fármacos de primeira e segunda linha contra a tuberculose, o que torna seu tratamento extremamente difícil. Este trabalho apresenta uma nova abordagem para sintetizar um híbrido de fármacos antituberculose: isoniazida (INH) e pirazinamida (PZA) A síntese foi realizada utilizando a síntese assistida por ultrassom de forma a obter um rendimento global de 70%, minimizando o tempo de reação de 7 h para ' h. A avaliação da atividade biológica do híbrido (composto 2) foi testada utilizando o ensaio de microplaca de tetrazólio (TEMA), mostrando uma inibição no crescimento de Mycobacterium tuberculosis H37Rv na concentração de 0,025 mM em pH 6,0 e 6,7.

Understanding colorectal twitter: A comparison of its highest and lowest rank influencers.

The distribution of content related to colorectal surgery in social media is steadily increasing. Social media influencers possess large audiences and are frequently viewed as authority; however, their credibility is often unchecked. In our commentary we present our analysis and comparison of the most and least influential accounts on Twitter within the field of colorectal surgery. Additionally, we discuss the current literature, role and importance of social media for the modern surgeon.

Impact of the COVID-19 pandemic during Spain's state of emergency on the diagnosis of colorectal cancer.

INTRODUCTION: We evaluate the impact of COVID-epidemic in colorectal cancer (CRC) diagnosis during Spain's state of emergency. METHODS: We compared newly diagnosed patients with patients diagnosed in the same period of 2019. RESULTS: A new diagnosis of CRC decreased 48% with a higher rate of patients diagnosed in the emergency setting (12.1% vs. 3.6%; p = .048) and a lower rate diagnosed in the screening program (5.2% vs. 33.3%; p = .000). CONCLUSIONS: Fewer patients have been diagnosed with CRC, with a higher rate of patients diagnosed in an emergency setting.

A Giant Childhood Mesenteric Lipoblastoma With Extensive Maturation.

Abdominal lipoblastomas are uncommon soft tissue tumors in children and rarely arise from the mesentery. Due to intraabdominal location and slow growth, these masses can go unnoticed for long periods of time and often found on surgical exploration. We present a case of a 12-year-old male with years of abdominal distension accompanied by new onset early satiety that was found to have an intra-abdominal mass. He underwent an exploratory laparotomy revealing a large 33 x 27 x 15 cm rubbery mesenteric mass displacing the entire intra-abdominal contents, connected by a single vascular pedicle and encasing a loop of small intestine. The mass was resected and the patient did well without signs of recurrence. Histology confirmed the presence of mature adipocytes but on further cytogenetic analysis, a translocation between chromosomes 2 and 8 at the 12q arm was detected, which is often associated with lipoblastomas. This case represents the one of the largest mesenteric lipoblastomas that matured extensively to lipoma-like histology at the time of surgical resection.

Phylogeny of Anopheles (Kerteszia) (Diptera: Culicidae) Using Mitochondrial Genes.

Identification of mosquito species is necessary for determining the entomological components of malaria transmission, but it can be difficult in morphologically similar species. DNA sequences are largely used as an additional tool for species recognition, including those that belong to species complexes. Kerteszia mosquitoes are vectors of human and simian malaria in the Neotropical Region, but there are few DNA sequences of Kerteszia species in public databases. In order to provide relevant information about diversity and improve knowledge in taxonomy of Kerteszia species in Peru, we sequenced part of the mitochondrial genome, including the cytochrome c oxidase I (COI) barcode region. Phylogenetic analyses structured all species of mosquitoes collected in Peru into a single clade, separate from the Brazilian species. The Peruvian clade was composed of two lineages, encompassing sequences from Anopheles Kerteszia boliviensis and Anopheles Kerteszia pholidotus. An. pholidotus sequences were recorded for the first time in Peru, whereas An. boliviensis sequences were for the first time published in the GenBank database. Sequences generated from specimens morphologically identified as Anopheles Kerteszia cruzii clustered into three separate clades according to the collection localities of Serra do Mar, Serra da Mantiqueira, and Serra da Cantareira, confirming An. cruzii as a species complex, composed of at least three putative species.

Reirradiación con radioterapia estereotáxica corporal (SBRT) en recidiva irresecable de cáncer de cabeza y cuello: a propósito de un caso / Re-irradiation with SBRT (Stereotactic Body Radiation Therapy) for locoregional unresectable relapse of head and neck cancer: a case report

Los pacientes con recidiva irresecable de un cáncer de cabeza y cuello (CCC) tienen un pronóstico desfavorable, con limitadas opciones de tratamiento. Los recientes avances técnicos permiten administrar la radioterapia (RT) con gran precisión, haciendo posible reirradiar tumores recidivados mediante radioterapia estereotáxica corporal (SBRT), administrando dosis elevadas de RT al mismo tiempo que se protegen los tejidos sanos próximos al tumor. Aunque esta técnica se ha utilizado para irradiar distintos tumores primarios y sus metástasis, la SBRT en cabeza y cuello ha tenido una evolución mucho más lenta que en otras localizaciones debido a las dificultades para reirradiar los CCC, por la toxicidad esperable al tratarse de una zona relativamente pequeña con gran vascularización e inervación, y donde se asientan varios sentidos. Presentamos el primer caso clínico de reirradiación con SBRT de una recidiva de un CCC en el Complejo Hospitalario de Navarra, que mostró respuesta completa y que permanece asintomático dieciséis meses después

Patients with an unresectable recurrence of head and neck carcinoma (HNC) have a poor prognosis, with limited treatment options. Recent technical advances allow radiotherapy (RT) to be handled with great precision, making it possible to re-irradiate recurrent tumors by means of stereotactic body radiotherapy (SBRT) with high doses of RT while protecting healthy tissues near the tumor. Although this technique has been used to irradiate different primary tumors and their metastases, SBRT in HNC has had a much slower evolution than in the mentioned locations. This is due to the difficulties in re-irradiating the HNC, because of the expected toxicity as it is a relatively small area with dense vascularization and innervation, and where several senses are located. We present the first case of a HNC re-irradiated with SBRT in the Complejo Hospitalario de Navarra; the patient showed a complete response and continues to be disease-free sixteen months after the irradiation

Further insight into the geographic distribution of Leishmania species in Peru by cytochrome b and mannose phosphate isomerase gene analyses.

To obtain further insight into geographic distribution of Leishmania species in Peru, a countrywide survey, including central to southern rainforest areas where information on causative parasite species is limited, was performed based on cytochrome b (cyt b) and mannose phosphate isomerase (mpi) gene analyses. A total of 262 clinical samples were collected from patients suspected of cutaneous leishmaniasis (CL) in 28 provinces of 13 departments, of which 99 samples were impregnated on FTA (Flinders Technology Associates) cards and 163 samples were Giemsa-stained smears. Leishmania species were successfully identified in 83 (83.8%) of FTA-spotted samples and 59 (36.2%) of Giemsa-stained smear samples. Among the 142 samples identified, the most dominant species was Leishmania (Viannia) braziliensis (47.2%), followed by L. (V.) peruviana (26.1%), and others were L. (V.) guyanensis, L. (V.) lainsoni, L. (V.) shawi, a hybrid of L. (V.) braziliensis and L. (V.) peruviana, and Leishmania (Leishmania) amazonensis. Besides the present epidemiological observations, the current study provided the following findings: 1) A hybrid of L. (V.) braziliensis and L. (V.) peruviana is present outside the Department of Huanuco, the only place reported, 2) Many cases of CL due to L. (V.) lainsoni, an uncommon causative species in Peru, were observed, and 3) L. (V.) shawi is widely circulating in southern Amazonian areas in Peru.

Radiopotentiation of enzalutamide over human prostate cancer cells as assessed by real-time cell monitoring.

AIM: To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells. BACKGROUND: While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. MATERIALS AND METHODS: Here, we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real-time cell analysis (RTCA), androgen-sensitive LNCaP cells (Lymph Node Carcinoma of the Prostate) and androgen-independent PC-3. Both cell lines were highly resistant to high doses of radiotherapy. RESULTS: A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade. CONCLUSIONS: These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.

GEORCC recommendations on target volumes in radiotherapy for Head Neck Cancer of Unkown Primary.

Head Neck Cancer of Unknown Primary (HNCUP) is a rare condition, representing approximately 5-10% of all head neck cancers. Radiotherapy, adjuvant or radical, is usually employed in the treatment of those patients. To date, no specific guidelines for the optimal definition of the target volume to be irradiated have been published. In recent years, there have been advances in the knowledge of the molecular biology of HNCUP, its diagnostic imaging and the implementation of sophisticated radiotherapy techniques with enhanced precision in target localization and treatment delivery. These progresses have provided valuable information about the natural history of HNCUP that will allow for establishment of the best treatment for each patient, including standardized, consistent and reproducible target volumes definitions. Several recommendations regarding how to choose volumes when contouring HNCUP in clinical practice are reported, in order to achieve a high rate of loco-regional control while avoiding unnecessary toxicity.